Author: "Service de Pathologie" - Searchworks@Jio Institute Digital Library Search Results

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2,188 results on '"Service de Pathologie"'

1. Ascaridiose

Author: Klotz, F, M’Baye, P.Saliou, and Wade, B
Published: 2004
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2. Explorations fonctionnelles dans le reflux gastro-œsophagien

Author: Farret, O., Thiolet, C., Mennecier, D., and Nizou, C.
Published: 2004
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3. Foie parasitaire

Author: Rey, P, Mbaye, P.-S, Debonne, J.-M, and Klotz, F
Published: 2004
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4. Determining PD-L1 Status in Patients With Triple-Negative Breast Cancer: Lessons Learned From IMpassion130

Author: Jary, Marine, Liu, Wen-Wei, Yan, Dongyao, Bai, Isaac, Muranyi, Andrea, Colle, Elise, Brocheriou, Isabelle, Turpin, Anthony, Radosevic-Robin, Nina, Bourgoin, Pierre, Penault-Llorca, Frédérique, Cohen, Romain, Vernerey, Dewi, André, Thierry, Borg, Christophe, Shanmugam, Kandavel, Svrcek, Magali, Liu, Wen‐wei, Cooperator Multidisciplinary Oncology Group (GERCOR), CHU Clermont-Ferrand, Ventana Medical Systems, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Saint-Antoine [AP-HP], Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Translational Cancer Research Unit [Antwerp], Philipps Universität Marburg = Philipps University of Marburg, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Division of Pathology and Laboratory Medicine, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), University of the Sunshine Coast (USC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Pathology, Aberdeen University Medical School, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), VU Medical Center, Cell Biology and Biotherapy Unit, INT-Fondazione Pascale, Department of Oncology and Metabolism [Sheffield, UK], The University of Sheffield [Sheffield, U.K.], Institute for Surgical Pathology, University hospital of Zurich [Zurich], Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Oncologie Médicale [CHU Saint -Antoine], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Oncologie Médicale [CHU Saint-Antoine], HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Cancer Research, Biopsy, Best practice, BluePrint 80-gene signature, Predictive, DNA Mismatch Repair, pMMR, B7-H1 Antigen, Cohort Studies, Breast cancer, MESH: Tumor Microenvironment, Tumor Microenvironment, MESH: B7-H1 Antigen, Prospective Studies, MESH: Lymphocytes, Tumor-Infiltrating, MESH: Cohort Studies, Oligometastatic colorectal cancer, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, high/low risk, immune profile, General Medicine, Immunohistochemistry, External quality assessment, 3. Good health, MESH: DNA Mismatch Repair, Oncology, Cytological techniques, Colonic Neoplasms, Molecular Medicine, HER2-low, Colorectal Neoplasms, PD-L1, Histology, Serum proteins, T lymphocytes, [SDV.CAN]Life Sciences [q-bio]/Cancer, Prognostic, Non-small cell lung carcinoma, Lymphocytes, Tumor-Infiltrating, Molecular diagnostics, Genetics, Humans, early breast cancer, MESH: Colonic Neoplasms, MESH: Humans, Liquid biopsy, gene expression profiles, MammaPrint 70-gene signature, Plasma proteins, Biomarker, MESH: Prospective Studies, digestive system diseases, Next-generation sequencing, Trastuzumab-deruxtecan, MESH: Tissue Fixation, hallmarks of cancer, MESH: Colorectal Neoplasms, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In the era of immune checkpoint inhibitors, understanding the metastatic microenvironment of proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is of paramount importance to both prognostication and the development of more effective novel therapies. In this study, primary and paired metastasis tissue samples were collected from patients with resectable metastatic CRC treated with adjuvant FOLFOX or peri-operative chemotherapy in the MIROX phase III prospective study. In total, 74 cancer tissues were stained for CD3, CD8, Forkhead box protein 3 (FOXP3), programmed cell death protein-1 (PD-1, invasive front, stromal, intra-epithelial compartments), and programmed death-ligand 1 (PD-L1, tumor, immune cells). The immune profiling of primary CRC had a limited value to predict the immune context of paired metastases for all markers but CD3+. The expression of CD8 and PD-L1 was higher in metastases after neoadjuvant FOLFOX. In metastases, both CD3 T cells at the invasive front and PD-L1 expressions on immune cells were predictive of better disease-free survival. These results show that the effect of FOLFOX on modifying the immune microenvironment in resected CRC metastases and measurement of PD-L1 expression and tumor-infiltrating CD8 T cells in pMMR/MSS metastatic tissue samples could improve treatment strategies of metastatic CRC patients.
Published: 2022

5. PACpAInt: a deep learning approach to identify molecular subtypes of pancreatic adenocarcinoma on histology slides

Author: C. Saillard, F. Delecourt, B. Schmauch, O. Moindrot, M. Svrcek, A. Bardier-Dupas, J-F. Emile, M. Ayadi, V. Rebours, L. de Mestier, P. Hammel, C. Neuzillet, J-B. Bachet, J. Iovanna, N. Dusetti, Y. Blum, M. Richard, Y. Kermezli, V. Paradis, M. Zaslavskiy, P. Courtiol, A. Kamoun, R. Nicolle, J. Cros, Owkin France, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de biologie cellulaire et moléculaire, Institut National de la Recherche Agronomique (INRA), Service de Pathologie [Clichy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: Pancreatic ductal adenocarcinoma (PAC) is a highly heterogeneous and plastic tumor with different transcriptomic molecular subtypes that hold great prognostic and theranostic values. We developed PACpAInt, a multistep approach using deep learning models to determine tumor cell type and their molecular phenotype on routine histological preparation at a resolution enabling to decipher complete intratumor heterogeneity on a massive scale never achieved before. PACpAInt effectively identified molecular subtypes at the slide level in three validation cohorts and had an independent prognostic value. It identified an interslide heterogeneity within a case in 39% of tumors that impacted survival. Diving at the cell level, PACpAInt identified “pure” classical and basal-like main subtypes as well as an intermediary phenotype and hybrid tumors that co-carried both classical and basal-like phenotypes. These novel artificial intelligence-based subtypes, together with the proportion of basal-like cells within a tumor had a strong prognostic impact.
Published: 2022

6. Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma

Author: Julien Calderaro, Luca Di Tommaso, Pascale Maillé, Aurélie Beaufrère, Cong Trung Nguyen, Lara Heij, Viviane Gnemmi, Rondell P. Graham, Frédéric Charlotte, Suzanne Chartier, Dominique Wendum, Mukul Vij, Daniela Allende, Alba Diaz, Carla Fuster, Benjamin Rivière, Astrid Herrero, Jérémy Augustin, Katja Evert, Diego Francesco Calvisi, Wei Qiang Leow, Howard Ho Wai Leung, Jan Bednarsch, Emmanuel Boleslawski, Mohamed Rela, Anthony Wing-Hung Chan, Alejandro Forner, Maria Reig, Anaïs Pujals, Loetitia Favre, Manon Allaire, Olivier Scatton, Arnaud Uguen, Eric Trépo, Lukas Otero Sanchez, Denis Chatelain, Myriam Remmelink, Camille Boulagnon-Rombi, Céline Bazille, Nathalie Sturm, Benjamin Menahem, Eric Frouin, David Tougeron, Christophe Tournigand, Emmanuelle Kempf, Haeryoung Kim, Massih Ningarhari, Sophie Michalak-Provost, Jakob Nikolas Kather, Annette S.H. Gouw, Purva Gopal, Raffaele Brustia, Eric Vibert, Kornelius Schulze, Darius F. Rüther, Sören A. Weidemann, Rami Rhaiem, Jean-Charles Nault, Alexis Laurent, Giuliana Amaddeo, Hélène Regnault, Eleonora de Martin, Christine Sempoux, Pooja Navale, Jayendra Shinde, Ketan Bacchuwar, Maria Westerhoff, Regina Cheuk-Lam Lo, Mylène Sebbagh, Catherine Guettier, Marie Lequoy, Mina Komuta, Marianne Ziol, Valérie Paradis, Jeanne Shen, Stefano Caruso, Hôpital Henri Mondor, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pathologie [Hôpital Beaujon - APHP], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université libre de Bruxelles (ULB), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Laboratoire de Signalisation et Récepteurs Matriciels (SiRMa), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de Pathologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Grenoble, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Viscérale et Digestive [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Johns Hopkins University (JHU), Hôpital Claude Huriez [Lille], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Labex OncoImmunology, Equipe labellisée Ligue Contre le Cancer, Université Paris Descartes - Paris 5 (UPD5), Service d'Hépatologie [Avicenne], Hôpital Avicenne [AP-HP], Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine [Bobigny], Université Paris 13 (UP13)-Sorbonne Paris Cité, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Crosscope, University of Michigan [Ann Arbor], University of Michigan System, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomie Pathologique [CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Labex Immuno-oncology [Paris] ( Université Paris Descartes - Paris 5 - PRES Sorbonne Paris Cité), Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Service d'Anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Henri Mondor, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], and Groningen Institute for Organ Transplantation (GIOT)
Subjects: Carcinoma, Hepatocellular, Hepatology, combined hepatocellular-cholangiocarcinoma, Liver Neoplasms, hepatocellular carcinoma, liver, Prognosis, Nestin, Cholangiocarcinoma, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, cancer, Humans, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background & Aims: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs.Methods: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling.Results: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA (“Nestin High”, >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies.Conclusion: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. Lay summary: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.
Published: 2021

7. Positive Association Between Location of Melanoma, Ultraviolet Signature, Tumor Mutational Burden, and Response to Anti–PD-1 Therapy

Author: Léa Dousset, Florence Poizeau, Caroline Robert, Sandrine Mansard, Laurent Mortier, Charline Caumont, Émilie Routier, Alain Dupuy, Jacques Rouanet, Maxime Battistella, Anna Greliak, David Cappellen, Marie-Dominique Galibert, Clara Allayous, Alexandra Lespagnol, Émilie Gerard, Inès Kerneuzet, Séverine Roy, Caroline Dutriaux, Jean-Philippe Merlio, Beatrice Vergier, Alexa B. Schrock, Jessica Lee, Siraj M. Ali, Solène-Florence Kammerer-Jacquet, Céleste Lebbé, Marie Beylot-Barry, Lise Boussemart, CHU Bordeaux [Bordeaux], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Lille, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Foundation Medicine Inc, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Dupuis, Christine, Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université Paris-Saclay, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Bordeaux (UB), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Foundation Medicine, Inc. [Cambridge, MA, USA], EQRX Inc [Cambridge, MA, USA], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Pathologie [Rennes] = Pathology [Rennes], Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)
Subjects: Cancer Research, [SDV]Life Sciences [q-bio], Infant, Newborn, ORIGINAL REPORTS, Cumulative sun exposure, B7-H1 Antigen, [SDV] Life Sciences [q-bio], Tumor mutational burden (TMB), Oncology, Child, Preschool, Mutation, Biomarkers, Tumor, Humans, Prospective Studies, Location of the primary melanoma, Precision Medicine, Melanoma
Abstract: PURPOSE Emerging evidence suggests a correlation between the tumor mutational burden (TMB) and the response to programmed cell death-1 protein (PD-1) monotherapy across multiple cancer types. In skin cancers, as high TMB is mostly because of ultraviolet (UV) exposure, we hypothesized a correlation between the primary melanoma cutaneous location according to sun exposure and response to anti–PD-1 monotherapy. METHODS The aim of this study was to analyze, in advanced melanoma, the relationship between TMB, locations according to sun exposure, and response to PD-1 inhibitors. We conducted a prospective multicentric analysis, by sequencing the most recent metastatic sample before PD-1 inhibitors using FoundationOne assay. RESULTS One hundred two patients were included, with TMB available for 94 cases. In univariate and multivariate linear regression, TMB was significantly associated with sun-exposed areas of the primary melanoma location and with age (coefficients of the association with log-TMB: non-UV location, –1.05; chronic sun-exposed area, 1.12; P value for the location, < 10–5; age, 0.021 per year, P value for age, .002). Molecular UV signature present on the metastatic site was associated with higher TMB (P = .003). Melanomas bearing a high TMB had a higher probability of response to PD-1 inhibitors compared with melanomas with a low TMB, with a dose-dependent effect following an exponential curve and a negative odds ratio of 0.40 (95% CI, 0.20 to 0.72, P = .004) between log-TMB and 6-month progression. CONCLUSION Cumulative sun exposure related to skin location and molecular UV signature present on the metastatic site appear to be relevant biomarkers directly linked to TMB. Because TMB is not yet available to all for routine clinical use, the location of the primary melanoma in a sun-exposed area may play an important role in clinical decisions regarding therapeutic choice., The location of the primary melanoma in a sun-exposed area can help choosing first-line advanced melanoma treatment.
Published: 2021

8. Clinical relevance of interdental papilla biopsy in chronic erosive gingivitis (desquamative gingivitis): retrospective bicentric study of 148 specimens

Author: Sébastien Jungo, Frédérick Gaultier, Gogly Bruno, François Le Pelletier de Clatigny, Sophie-Myriam Dridi, Fadel Bellakhdar, Philippe Pirnay, Saskia Ingen-Housz-Oro, Anne-Laure Ejeil, CHU Henri Mondor, Service d'Odontologie [Bretonneau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bretonneau, Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Biopsy, Autoimmune bullous diseases, Gingiva, Diagnosis, Differential, 030207 dermatology & venereal diseases, 03 medical and health sciences, Gingivitis, 0302 clinical medicine, Biopsy Site, medicine, Humans, General Dentistry, Interdental papilla, Retrospective Studies, medicine.diagnostic_test, business.industry, Research, Postoperative complication, RK1-715, 030206 dentistry, medicine.disease, Dermatology, 3. Good health, Desquamative gingivitis, medicine.anatomical_structure, Dentistry, Erosive gingivitis, Oral lichen planus, Oral and maxillofacial surgery, medicine.symptom, Differential diagnosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Chronic erosive gingivitis, also called desquamative gingivitis, defines a clinical picture that can be generated by several inflammatory and immune diseases. Pathology is therefore essential for the differential diagnosis. However, when the gingival lesion is initial, exclusive or predominant, selecting the biopsy site and protocol may be problematic due to tissue fragility. Especially since there are few studies on the subject, the aim of our study was to assess the protocol, diagnostic relevance and tolerance of an original protocol using interdental papilla biopsy. Methods We conducted a retrospective bicentric study, from October 2011 to July 2019, including all patients with a chronic erosive gingivitis who had received, for diagnostic purposes, a interdental papilla biopsy. Results The contribution levels for the two hospital departments were 94.7% and 97.1%, respectively. No postoperative complication was recorded in the short or long term. Conclusion The interdental papilla biopsy protocol is perfectly adapted to the anatomopathological examinations required to establish differential diagnosis of chronic erosive gingivitis. This surgical protocol is simple to perform, non iatrogenic with a very good tolerance and and accessible to all clinicians. It is highly efficient with an excellent contribution level. ClinicalTrials NCT04293718 (March 3, 2020). Health Data Hub N° F20201109083211 (November 9, 2020).
Published: 2021

9. PD-L1 (SP142) testing is concordant between Benchmark Ultra and Bond-III stainers

Author: Morgan Rouprêt, Eva Compérat, André Oszwald, Justine Wacquet, Olivier Cussenot, Gabriel Wasinger, Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Groupe de Recherche Clinique Onco-Urologie Prédictive [CHU Tenon] (GRC 5), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Medizinische Universität Wien = Medical University of Vienna, Service de Pathologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service d'urologie [CHU Tenon]
Subjects: Urology, Tumor cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Atezolizumab, PD-L1, Medicine, Humans, Stage (cooking), Coloring Agents, Clinical pathology, 030304 developmental biology, 0303 health sciences, PD-L1 inhibitors, Bladder cancer, biology, Staining and Labeling, business.industry, Equipment Design, medicine.disease, Topic Paper, Immunohistochemistry, 3. Good health, Metastatic bladder cancer, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, biology.protein, business, Nuclear medicine, Kappa
Abstract: Background Atezolizumab is an inhibitor of programmed death-ligand 1 (PD-L1), used to treat advanced or metastatic bladder cancer, and in trials for non-invasive disease. In order to be eligible for treatment, patients require a PD-L1 immune cell score ≥ 5%, using the Ventana SP142 PD-L1 assay. Many laboratories do not have access to the required Ventana Benchmark Ultra stainer, and it is unclear if the assay performs similarly on other stainers. In this study, we compare SP142 assay results between Ventana Benchmark Ultra and Leica Bond-III stainers. Methods Serial sections of 90 samples of transurethral bladder resections (comprising 51 pTaHG, 8 pTis, 18 pT1, 10 pT2 tumors) were stained using the SP142 PD-L1 antibody on Ventana Benchmark Ultra and Leica Bond-III stainers, manually scored, and compared using accuracy and Cohen’s kappa measures. Results Both devices yielded highly concordant PD-L1 immune cell scores (accuracy 0.84, Cohen’s κ 0.732). Moreover, we found similar tumor cell (TC) PD-L1 scores using both stainers, and a trend towards greater TC scores in pT2 stage samples (p = 0.05). Conclusion This study is the first to compare the SP142 antibody in bladder cancer on two different stainers. Our results indicate that both Benchmark Ultra and Bond-III stainers yield highly concordant results using the SP142 PD-L1 antibody.
Published: 2021

10. Renal toxicities associated with pembrolizumab

Author: David Malka, Alexis Mathian, Olivier Lambotte, Hassan Izzedine, Zahir Amoura, Andrea Varga, Sihem Kaaki, Christine Mateus, Alexandra Leary, Jean-Charles Soria, Isabelle Brocheriou, Aurélien Marabelle, Stéphane Champiat, Jean-Michel Goujon, Emilie Routier, Cécile Picard, Nathalie Quellard, Judith Michels, Jean-Marie Michot, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Interdisciplinaire de Soins de Support aux Patients en Onco-hématologie [Gustave Roussy] (DISSPO), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Oncologie digestive, Oncologie gynécologique, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de pathologie [CHU Pitié-Salpêtrière]
Subjects: Nephrology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030232 urology & nephrology, Renal function, Pembrolizumab, Gastroenterology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Minimal change disease, Drug-Induced Nephropathies, Dialysis, Transplantation, Kidney, minimal change nephropathy, business.industry, Acute kidney injury, medicine.disease, acute tubular injury, 3. Good health, medicine.anatomical_structure, acute kidney injury, acute interstitial nephritis, pembrolizumab, business
Abstract: International audience; Objective : Expanded clinical experience with patients treated by pembrolizumab has accumulated. However, renal toxicities associated with this anti-programmed cell death 1 agent are poorly described because kidney histology is rarely sought. As a nephrology referral centre, we aimed to describe the clinic-biological and histopathological characteristics of pembrolizumab-related nephropathy and its response to treatment.Methods : We conducted a monocentric large case series study, including all pembrolizumab-treated cancer patients presenting a renal toxicity addressed to our centre from 2015 to 2017.Results : A total of 12 patients (7 men) out of 676 pembrolizumab-treated patients (incidence 1.77%) were included (median age 69.75 years). Patients were referred for acute kidney injury (n = 10) and/or proteinuria (n = 2). A kidney biopsy was performed in all patients, with a median duration of use of 9 months (range 1-24 months) after the beginning of treatment. Biopsy showed that four patients had acute interstitial nephritis (AIN), whereas five had acute tubular injury (ATI) alone, one had minimal change disease (MCD) and ATI, and one had MCD alone. Pembrolizumab withdrawal coupled with corticosteroid therapy was the most effective treatment for kidney function recovery. Drug reintroduction resulted in a more severe recurrence of AIN in one patient who required maintenance of pembrolizumab. Two patients died of cancer progression with one of them developing severe renal failure requiring dialysis.Conclusion : In our series, ATI, AIN and MCD are the most frequent forms of kidney involvement under pembrolizumab therapy. Kidney dysfunction is usually isolated but can be severe. Use of corticosteroids in case of AIN improves the glomerular filtration rate.
Published: 2018

11. Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features

Author: Jean-François Emile, Jean-Luc Van Laethem, Jérôme Torrisani, Pieter Demetter, Yuna Blum, Anne Couvelard, Pascal Hammel, Armelle Bardier-Dupas, Francesco Puleo, Miroslaw Radman, Jérôme Cros, Magali Svrcek, Rémy Nicolle, Jerome Raffenne, Valérie Paradis, Fernando Ariel Martin, Marina Konta, Jean-Baptiste Bachet, Vinciane Rebours, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Ambroise Paré [AP-HP], Hôpital Erasme [Bruxelles] (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Cancer Research, DNA repair, [SDV]Life Sciences [q-bio], Young patients, Biology, elderly patients, Multi‐omics, lcsh:RC254-282, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine, Epigenomics, Two-dimensional gel electrophoresis, PDAC, Methylation, Sciences bio-médicales et agricoles, multi-omics, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV] Life Sciences [q-bio], Cancérologie, Elderly patients, young patients, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Proteome, Cancer research, Adenocarcinoma
Abstract: Pancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late‐onset tumors (LOT) have been described, little is known about early‐onset tumors (EOT). Ageing is known to impact DNA methylation and proteome integrity through carbonylation‐related oxidative damages. We therefore aimed to assess the global molecular features of EOT. We compared 176 EOT (≤55 y.o.) and 316 LOT (≥70 y.o.) from three distinct surgical cohorts at the clinical/genomic/epigenomic/transcriptomic level. Furthermore, we assessed oxidative stress responses and oxidative proteome damages using 2D gel electrophoresis followed by mass spectrometry protein identification. There was no consistent clinical difference between EOT and LOT across the three cohorts. The mutational landscape of key driver genes and the global methylation profile were similar in the two groups. LOT did display age‐related features such as enriched DNA repair gene signatures and upregulation of oxidative stress defenses together with increased proteome carbonylation. However, these age‐related differences were more preeminent in non‐tumor tissues while tumor proteome and proteome damages were fairly comparable. In conclusion, this multiomics comparison showed that EOT harbor a comparable molecular profile to that of LOT., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021
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12. CARMN-NOTCH2 fusion transcript drives high NOTCH2 expression in glomus tumors of the upper digestive tract

Author: Janick Selves, Jean-François Emile, Marie Laure Raffin-Sanson, Benoǐt Terris, Chiara Villa, Nicolas Girard, Jérôme Cros, Catherine Julie, Jean François Fléjou, Zofia Hélias-Rodzewicz, Jean Michel Coindre, Christine Lagorce-Pages, Anne Sophie de Lajarte-Thirouard, Nathalie Guedj, Florence Renaud, Dominique Cazals-Hatem, Simon Martin de Beauce, Cristi Marin, Henri Jean Garchon, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Foch [Suresnes], CHU Pontchaillou [Rennes], Centre hospitalier [Valenciennes, Nord], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service d’Anatomie Pathologique [CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’endocrinologie et nutrition [AP-HP Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Bergonié [Bordeaux], UNICANCER, Validation et identification de nouvelles cibles en oncologie (VINCO), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Association Pour la Recherche et L'enseignement en Pathologie, AREP, The study was supported by grants from Association pour la Recherche et l'Enseignement en Pathologie (AREP). The authors would like to thank Nathalie Terrones, Dominique Pechaud, Véronique Toulza, and Tristan Robert for performing tissue arrays sections and immunohistochemistry., École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Cancer Research, Pathology, medicine.medical_specialty, endocrine system, endocrine system diseases, translocation, Chromosomal translocation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, digestive tract, Fusion gene, 03 medical and health sciences, CARMN, 0302 clinical medicine, NOTCH2, Biomarkers, Tumor, Genetics, medicine, Humans, Receptor, Notch2, Gene, Exome, Gastrointestinal Neoplasms, 030304 developmental biology, 0303 health sciences, Stomach, medicine.disease, Phenotype, Glomus tumor, MicroRNAs, medicine.anatomical_structure, Fusion transcript, glomus tumor, 030220 oncology & carcinogenesis, Gene Fusion
Abstract: International audience; Glomus tumors (GTs) are perivascular tumors mostly occurring in the distal extremities. Rare cases arise in the digestive tract and may be misdiagnosed with neuroendocrine or gastrointestinal stromal tumors. We aimed to specify the features of GT of the upper digestive tract. Clinical, histological, phenotypic, and molecular features of 16 digestive GTs were analyzed, of whom two underwent whole exome and RNA sequencing to search for gene alterations. RNA-sequencing disclosed a t(1:5)(p13;q32) translocation, which resulted in the fusion of CARMN and NOTCH2 in two GTs. The fusion gene encoded a protein sequence corresponding to the NOTCH2 intracellular domain that functions as transcription factor. These finding was supported by high expression of genes targeted by NOTCH. The CARMN-NOTCH2 translocation was detected in 14 out of 16 (88%) GTs of the upper digestive tract; but in only in two out of six cutaneous GTs (33%). Most digestive GT arose from the stomach (n = 13), and the others from duodenal (2) or oesophagous (1). Nuclear expression of NOTCH2 was detected in the 14 cases containing the fusion transcripts. The CARMN-NOTCH2 fusion transcript may contribute to activation of the NOTCH2 pathway in GT and drive tumor development. The high frequency of this translocation in GT of the upper digestive track suggest that detection of nuclear NOTCH2 expression may be useful diagnostic biomarker of these tumors.
Published: 2021

13. Chemotherapy in resected neuroendocrine carcinomas of the digestive

Author: Pellat, Anna, Walter, Thomas, Augustin, Jeremy, Hautefeuille, Vincent, Hentic, Olivia, Do Cao, Christine, Lièvre, Astrid, Coriat, Romain, Hammel, Pascal, Dubreuil, Olivier, Cohen, R., Couvelard, A., André, T., Svrcek, M, Baudin, Emmanuel, Afchain, P., Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'endocrinologie pédiatrique [CHU Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Curie [Paris], Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes], CHU Pontchaillou [Rennes], Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cooperator Multidisciplinary Oncology Group (GERCOR), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Département d'Anatomo-Pathologie [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Pathologie [CHU Saint-Antoine], Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Service d’anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Service d'hépato-gastro-entérologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Gestionnaire, HAL Sorbonne Université 5, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Oncologie Médicale [CHU Saint-Antoine], Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: ki-67 index 43 44 2, [SDV.CAN] Life Sciences [q-bio]/Cancer, neuroendocrine carcinomas, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemotherapy
Abstract: International audience; Background: Neuroendocrine carcinomas (NECs) of the digestive tract are rare and aggressive tumours. In localised disease the treatment is surgery. Based on expert consensus, international guidelines recommend the administration of adjuvant chemotherapy combining etoposide and platinum derivatives, justified by the high risk of metastatic relapse. However, no clinical study has proven the benefit of neoadjuvant or adjuvant chemotherapy. Objectives: We aimed to evaluate the effect of neoadjuvant +/– adjuvant and adjuvant therapy in this indication. Methods: We performed a retrospective observational French study to evaluate overall survival (OS) and disease-free survival (DFS), prognostic factors for survival, and chemotherapy toxicity. Results: Seventy-three patients had surgical resection of a localised digestive NEC between January 1, 2000 and December 31, 2016. The majority of patients presented colorectal (35%) tumours and the median Ki-67 value was 70%. Forty-three patients received chemotherapy, either perioperative (neoadjuvant +/– adjuvant) or adjuvant. The median OS and DFS for the whole population was 24 and 9 months, respectively. The median OS and DFS for patients receiving chemotherapy was 62 and 13 months, respectively. Positive postoperative node status and Ki-67 ≥80% had a negative prognostic impact on OS and DFS. Administration of chemotherapy had a positive prognostic impact on OS and DFS. Sixteen grade 3/4 toxicities were reported without toxic death. Conclusions: Our results suggest a positive effect on survival of chemotherapy in resected digestive NECs, but further studies are needed to confirm these results.
Published: 2020

14. HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma

Author: Sonigo, Gabrielle, Battistella, Maxime, Beylot-Barry, Marie, Ingen-Housz-Oro, Saskia, Franck, Nathalie, Barète, Stéphane, Boulinguez, Serge, Dereure, Olivier, Bonnet, Nathalie, Brice, Pauline, Boccara, Olivia, Bodemer, Christine, Adamski, Henri, D'Incan, Michel, Ortonne, Nicolas, Fraitag, Sylvie, Brunet-Possenti, Florence, Dalle, Stéphane, Suarez, Felipe, Skowron, François, Haidar, Dima, Maubec, Eve, Bohelay, Gerome, Laroche, Liliane, Mahé, Antoine, Birckel, Elodie, Bouaziz, Jean-David, Brocheriou, Isabelle, Dubois, Romain, Faiz, Sarah, Fadlallah, Jehane, Ram-Wolff, Caroline, Carlotti, Agnès, Bens, Guido, Balme, Brigitte, Vergier, Béatrice, Laurent-Roussel, Sara, Deschamps, Lydia, Carpentier, Olivier, Moguelet, Philippe, Herve, Genevieve, Comoz, Francois, Le Gall, François, Leverger, Guy, Finon, Antoine, Augereau, Olivier, Blechet, Claire, Kerdraon, Rémy, Lamant, Laurence, Tournier, Emilie, Franck, Frédéric, Costes-Martineau, Valérie, Szablewski, Vanessa, Taix, Sebastien, Beschet, Isabelle, Guérin, Frédéric, Sepulveda Garrido, Fernando, Bagot, Martine, De Saint Basile, Geneviève, Michonneau, David, de Masson, Adèle, Socié, Gérard, Bodemer, Shristine ChB, Marçais, Ambroise, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Henri Mondor, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Hôpital Nord [CHU - APHM], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre Hospitalier de Valence (CH DE VALENCE), Centre hospitalier de Valence, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Avicenne [AP-HP], Hôpital pasteur [Colmar], Service de Dermatologie [AP-HP Hôpital Saint-Louis], Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), Mouvement, Équilibre, Performance, Santé (MEPS), Université de Pau et des Pays de l'Adour (UPPA), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Service de pathologie [CHU Bichat], Service d’Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire d'aérologie (LAERO), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d’anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre Hospitalier Régional d'Orléans (CHR), Laboratoire d'aérologie (LA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunithérapie (HIPI (UMR_S_976 / U976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Anatomie et cytologie pathologiques [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COLO, Mouniati, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, medicine.medical_specialty, Panniculitis, [SDV]Life Sciences [q-bio], Immunology, 2 supplemental tables, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymphoma, T-Cell, HAVCR2, Biochemistry, Lymphohistiocytosis, Hemophagocytic, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Subcutaneous Panniculitis-Like T-Cell Lymphoma, 9 references Article type: Letter Scientific category: Lymphoma, Humans, Medicine, Genetic Predisposition to Disease, Hepatitis A Virus Cellular Receptor 2, Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Hemophagocytic lymphohistiocytosis, business.industry, Cell Biology, Hematology, medicine.disease, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], 1 supplemental figure, 030220 oncology & carcinogenesis, Mutation, Mutation (genetic algorithm), 2 tables, Female, business, Biomarkers
Abstract: International audience
Published: 2020

15. A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation

Author: Benjamin Bonhomme, Cleofe Romagosa, Gaëlle Pierron, Anne Moreau, Jean Michel Coindre, Arjen H.G. Cleven, Irma Ramos-Oliver, François Le Loarer, Sophie Le Guellec, Corinne Bouvier, Sébastien Salas, Anne Gomez-Brouchet, Virginie Audard, Marie Pierre Castex, Frédérique Larousserie, Anand Sherwood, Anne-Marie Cleton-Jansen, Dilara C. Savci-Heijink, Camille Laurent, Franck Tirode, Judith V.M.G. Bovée, Daniel Pissaloux, Jessica Baud, Antoine Giraud, Herman M. Kroon, Institut Bergonié [Bordeaux], UNICANCER, Université de Bordeaux (UB), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Leiden University Medical Center (LUMC), Département de pathologie [CHU La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'oncologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], Vall d'Hebron University Hospital [Barcelona], Service de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [AP-HP Hôpital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biologie des Tumeurs, Institut Curie [Paris], Department of Conservative Dentistry and Endodontics [CSI College of Dental Sciences, Madurai, India], Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and TIRODE, Franck
Subjects: Male, 0301 basic medicine, Pathology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Fusion gene, 0302 clinical medicine, CDKN2A, Rhabdomyosarcoma, Anaplastic Lymphoma Kinase, Prospective Studies, Child, Exome, Aged, 80 and over, medicine.diagnostic_test, Epithelioid Cells, Soft tissue, Middle Aged, Prognosis, Immunohistochemistry, Up-Regulation, 3. Good health, DNA-Binding Proteins, Phenotype, Molecular Diagnostic Techniques, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Sarcoma, Gene Fusion, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Craniofacial, Retrospective Studies, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, 030104 developmental biology, Transcription Factors, Fluorescence in situ hybridization
Abstract: International audience; Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n = 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient's age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n = 12/14) and soft tissue (n = 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n = 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALK fusion on break-apart FISH (n = 5) nor next-generation sequencing (n = 14). ALK upregulation was frequently associated with an internal deletion at genomic level. TFCP2 was fused in 5' either to EWSR1 (n = 6) or FUS (n = 8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n = 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2A deletions. FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.
Published: 2020

16. Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry

Author: Nicolas Franck, E. Maubec, Gaëlle Quéreux, Caroline Ram-Wolff, Philippe Courville, Laurence Lamant, Olivier Dereure, G. Dobos, Isabelle Templier, Florent Grange, Saskia Ingen-Housz-Oro, Jacques Rouanet, Martine Bagot, N. Josselin, O. Augereau, Stéphane Barete, Serge Boulinguez, Isabelle Moulonguet, Marisa Battistella, Nicolas Ortonne, Anne Durlach, A. Carlotti, Pascal Joly, S. Taix, Sophie Dalac, Michel D'Incan, F. Franck, Laurent Mortier, A. de Masson, Marie Beylot-Barry, Charlée Nardin, Jacqueline Rivet, M.-D. Vignon-Pennamen, Laurence Michel, Liliane Laroche, Anne Pham-Ledard, Romain Dubois, T. Petrella, Béatrice Vergier, Florent Amatore, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Cochin [AP-HP], Centre hospitalier de Cahors, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Dermatologie (CHU de Dijon), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Grenoble, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Cahors, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: medicine.medical_specialty, Mycosis fungoides, Heterogeneous group, business.industry, Incidence (epidemiology), [SDV]Life Sciences [q-bio], CBCL, Retrospective cohort study, Dermatology, medicine.disease, Cutaneous lymphoma, 3. Good health, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Male patient, Epidemiology, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Background Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. Objectives The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. Methods Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. Results The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. Conclusions Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.
Published: 2020

17. Ovarian and peritoneal psammocarcinoma: Results of a multicenter study on 25 patients

Author: Jean-Baptiste Delhorme, Jordan Ohayon, Sébastien Gouy, Gerlinde Averous, Catherine Genestie, Léopold Gaichies, Olivier Glehen, Jean-Marc Guilloit, Denis Pezet, Francois Quenet, Gwenaël Ferron, Cécile Brigand, Philippe Morice, Charles Honoré, Julio Abba, Karine Abboud, Mohammad Alyami, Catherine Arvieux, Naoual Bakrin, Gisèle Balagué, Vincent Barrau, Houda Ben Rejeb, Jean-Marc Bereder, Isabelle Berton-Rigaud, Frédéric Bibeau, Isabelle Bonnefoy, Dominique Bouzard, Ivan Bricault, Sébastien Carrère, Cécile de Chaisemartin, Madleen Chassang, Anne Chevallier, Thomas Courvoisier, Peggy Dartigues, Anthony Dohan, Julien Dubreuil, Frédéric Dumont, Clarisse Eveno, Marie Faruch-Bilfeld, Juliette Fontaine, Laure Fournier, Johan Gagniere, Delphine Geffroy, Laurent Ghouti, François-Noël Gilly, Laurence Gladieff, Diane Goéré, Aymeric Guibal, Frédéric Guyon, Bruno Heyd, Christine Hoeffel, Constance Hordonneau, Sylvie Isaac, Peggy Jourdan-Enfer, Rachid Kaci, Reza Kianmanesh, Catherine Labbé-Devilliers, Joëlle Lacroix, Bernard Lelong, Agnès Leroux-Broussier, Yoann Lherm, Réa Lo Dico, Gérard Lorimier, Caroline Malhaire, Frédéric Marchal, Pascale Mariani, Emilie Mathiotte, Pierre Meeus, Eliane Mery, Simon Msika, Cédric Nadeau, Pablo Ortega-Deballon, Guillaume Passot, Olivier Pellet, Patrice Peyrat, Nicolas Pirro, Marc Pocard, Flora Poizat, Jack Porcheron, Anaïs Poulet, François Quenet, Patrick Rat, Pierre Rousselot, Pascal Rousset, Hélène Senellart, Martine Serrano, Vincent Servois, Olivia Sgabura, Andrea Skanjeti, Magali Svrcek, Raphaël Tetreau, Emilie Thibaudeau, Yann Touchefeu, Jean-Jacques Tuech, Séverine Valmary-Degano, Delphine Vaudoyer, Stéphane Velasco, Véronique Verriele-Beurrier, Laurent Villeneuve, Romuald Wernert, Franck Zinzindohoue, Département de chirurgie générale et digestive [CHU Strasbourg], Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Institut Gustave Roussy (IGR), Département de chirurgie gynécologique [Gustave Roussy], Service d'anatomie pathologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Nord, Hôpital nord, Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Grenoble, Hôpitaux Universitaires de Strasbourg, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Laboratoire d'anatomo-pathologie, CRLCC Val d'Aurelle - Paul Lamarque, Département de chirurgie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département de biologie et pathologie médicales [Gustave Roussy], Department of Body and Interventional Imaging, Hôpital Lariboisière, Paris, France., Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Toulouse [Toulouse], Institut Claudius Regaud, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hospices Civils de Lyon (HCL), Département de chirurgie générale [Gustave Roussy], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service de chirurgie viscérale et digestive - Unité de transplantation hépatique, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Radiologie, Service de pathologie, Service de Chirurgie Générale, Digestive et Endocrine [CHU Reims], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de Radiologie [CLCC Baclesse], Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherches (CRT), Société Lafarge, Service de Chirurgie d'Oncologie Digestive [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Paul Papin(Angers), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Centre Léon Bérard [Lyon], Institut Claudius Regaud. Department of pathology, Hôpital Louis Mourier - AP-HP [Colombes], Department of Gynecology and Obstetrics, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Chirurgie Digestive (AP-HM), Université de la Méditerranée - Aix-Marseille 2, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Biopathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Chirurgie digestive, Centre Hospitalier Universitaire de Saint-Etienne, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), CRLC Val d'Aurelle-Paul Lamarque, Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Anatomie Pathologique, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Radiology, Centre René Gauducheau, CRLCC René Gauducheau, Université de Lyon, (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Institut du Cancer de Montpellier (ICM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'éthique médicale et médecine légale (LEM), Université Paris Descartes - Paris 5 (UPD5), Service de Pathologie, Centro de Investigaciones Oceanograficas e Hidrograficas (CIOH), DIMAR, Ministerio de Defensa Nacional, Colombie, Unité de Méthodologie en Recherche Clinique, Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL), Service de chirurgie digestive, générale et cancérologique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), and Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP]
Subjects: Hyperthermic Intraperitoneal Chemotherapy, Intraperitoneal chemotherapy, chemistry.chemical_compound, 0302 clinical medicine, Infusions, Parenteral, Peritoneal Neoplasms, Ovarian Neoplasms, Univariate analysis, 030219 obstetrics & reproductive medicine, General Medicine, Cytoreduction Surgical Procedures, Middle Aged, Neoadjuvant Therapy, Progression-Free Survival, 3. Good health, Survival Rate, medicine.anatomical_structure, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, France, Peritoneum, Pancreas, Adult, medicine.medical_specialty, Adolescent, Ovary, Antineoplastic Agents, Psammocarcinoma, 03 medical and health sciences, Young Adult, medicine, Humans, Aged, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carboplatin, Surgery, chemistry, Multicenter study, Conventional PCI, Neoplasm Grading, business, Neoplasms, Cystic, Mucinous, and Serous, Rare disease
Abstract: International audience; Purpose: Psammocarcinoma (PK) is a rare disease of unknown origin. We aimed to report the characteristics, management and survival of patients operated on for PK within the French Network for Rare Peritoneal Malignancies (RENAPE) expert centers.Patients and methods: All consecutive cases of PK operated within all 26 RENAPE centers between 1997 and 2018 were retrospectively analyzed.Results: Twenty-five patients were identified. The median age was 53 years [range 17–78]. None of the patients had extra peritoneal metastases at diagnosis. A median of 6 cycles of carboplatin-based systemic chemotherapy was delivered in 52% preoperatively (n = 13) and 56% postoperatively (n = 14); associated with placlitaxel for 12 patients. All patients were operated on. The median PCI was 23 [0–33]. Eighty-four percent had a complete cytoreductive surgery through digestive (n = 7), spleen (n = 3), pancreas (n = 1) resections and/or multiple peritonectomies (n = 11). Five patients (20%) had intraperitoneal chemotherapy. Morbidity (Dindo-Clavien ≥3) was 12%. No postoperative death occurred. After a median follow-up of 42 months (range [2–194]), the median overall (OS) and progression-free (DFS) survival times were respectively 128 months and 31 months. Eighteen patients recurred (72%), mainly in the peritoneum (n = 16). Four of them (22%) were reoperated. The 5 and 10-year DFS rates were both 20.3%. The 5 and 10-year OS rates were 62% and 51.7%, respectively. A complete cytoreductive surgery was associated with a better OS and DFS in a univariate analysis.Conclusion: Complete cytoreductive surgery is the cornerstone of the PK's management as a primary treatment. Recurrence remains common and new adjuvant strategies seem needed.
Published: 2019

18. Detection of the Merkel cell polyomavirus in the neuroendocrine component of combined Merkel cell carcinoma

Author: Mahtab Samimi, Serge Guyétant, Yannick Le Corre, David Schrama, Antoine Touzé, Hervé Maillard, Thibault Kervarrec, Tarik Gheit, Roland Houben, Patrick Michenet, Pauline Gaboriaud, Gaëlle Fromont, Eva Hainaut-Wierzbicka, Adeline Furudoï, Massimo Tommasino, Guido Bens, François Aubin, Agnès Beby-Defaux, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Service de Pathologie, Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), University Hospital of Würzburg, Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), International Agency for Research on Cancer (IARC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Récepteurs, Régulations, Cellules Tumorales (2RCT), Université de Poitiers, Service de Dermatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de pathologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Cancéropôle du Grand Sud-Ouest, Centre Hospitalier Régional d'Orléans (CHRO), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Hôpital René HUGUENIN (Saint-Cloud)-Institut Curie [Paris], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, Skin Neoplasms, medicine.medical_treatment, Merkel cell polyomavirus, medicine.disease_cause, Pathology and Forensic Medicine, 030207 dermatology & venereal diseases, 03 medical and health sciences, Cytokeratin, Merkel cell carcinoma, 0302 clinical medicine, medicine, Humans, Molecular Biology, Aged, Aged, 80 and over, Squamous carcinoma, biology, business.industry, food and beverages, Cancer, Immunosuppression, Cell Biology, General Medicine, Papillomavirus, biology.organism_classification, medicine.disease, 3. Good health, Carcinoma, Merkel Cell, Combined merkel cell carcinoma, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cancer research, Female, Polyomavirus, Carcinogenesis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CD8
Abstract: The online version of this article ( https://doi.org/10.1007/s00428-018-2342-0) contains supplementary material, which is available to authorized users.; International audience; Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities. In this study, we aimed to determine the viral status of combined MCC by a multimodal approach. We histologically reviewed 128 cases of MCC and sub-classified them as "combined" or "conventional." Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12 cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC were investigated for MCPyV viral status by combining two independent molecular procedures. Furthermore, on multiplex genotyping assay, the samples were examined for the presence of other polyoma- and papillomaviruses. Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With the molecular procedure, half of the combined MCC cases were positive for MCPyV in the neuroendocrine component. Beta papillomaviruses were detected in 5/8 combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection of MCPyV DNA in half of the combined MCC cases suggests similar routes of carcinogenesis for combined and conventional MCC.
Published: 2018

19. Multicenter Evaluation of a Novel ROS1 Immunohistochemistry Assay (SP384) for Detection of ROS1 Rearrangements in a Large Cohort of Lung Adenocarcinoma Patients

Author: Sandra Lassalle, Jean-Christophe Sabourin, Elodie Long-Mira, Julien Mazieres, Frédéric Bibeau, Michel Poudenx, Salomé Lalvée, Jonathan Benzaquen, Charles-Hugo Marquette, Jean Michel Vignaud, Paul Hofman, Simon Heeke, Hugues Begueret, Katia Zahaf, Anne-Laure Lepage, Nicolas Piton, Emmanuel Chamorey, Clémence Yguel, Marius Ilie, Véronique Hofman, Isabelle Rouquette, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de Pathologie Clinique et Expérimentale. Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), CHU Toulouse [Toulouse], Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Pathologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de pathologie [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Lung adenocarcinoma, medicine.medical_specialty, Lung Neoplasms, Interclass correlation, Clone (cell biology), Adenocarcinoma of Lung, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Proto-Oncogene Proteins, Internal medicine, Biomarkers, Tumor, medicine, ROS1, Humans, D4D6, In Situ Hybridization, Fluorescence, Retrospective Studies, Gene Rearrangement, medicine.diagnostic_test, business.industry, Molecular pathology, Fluorescence in situ hybridization, Gold standard (test), Protein-Tyrosine Kinases, Prognosis, medicine.disease, Immunohistochemistry, SP384, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Adenocarcinoma, business, Follow-Up Studies
Abstract: Introduction The detection of a ROS1 rearrangement in advanced and metastatic lung adenocarcinoma (LUAD) led to a targeted treatment with tyrosine kinase inhibitors with favorable progression-free survival and overall survival of the patients. Thus, it is mandatory to screen for the ROS1 rearrangement in all these patients. ROS1 rearrangements can be detected using break-apart fluorescence in situ hybridization (FISH), which is the gold standard; however, ROS1 immunohistochemistry (IHC) can be used as a screening test because it is widely available, easy and rapid to perform, and cost-effective. Methods We evaluated the diagnostic accuracy and interpathologist agreement of two anti-ROS1 IHC clones, SP384 (Ventana, Tucson, Arizona) and D4D6 (Cell Signaling, Danvers, Massachusetts), in a training cohort of 51 positive ROS1 FISH LUAD cases, and then in a large validation cohort of 714 consecutive cases of LUAD from six routine molecular pathology platforms. Results In the two cohorts, the SP384 and D4D6 clones show variable sensitivity and specificity rates on the basis of two cutoff points greater than or equal to 1+ (all % tumor cells) and greater than or equal to 2+ (>30% stained tumor cells). In the validation cohort, the D4D6 yielded the best accuracy for the presence of a ROS1 rearrangement by FISH. Interpathologist agreement was moderate to good (interclass correlation 0.722–0.874) for the D4D6 clone and good to excellent (interclass correlation: 0.830–0.956) for the SP384 clone. Conclusions ROS1 IHC is an effective screening tool for the presence of ROS1 rearrangements. However, users must be acutely aware of the variable diagnostic performance of different anti-ROS1 antibodies before implementation into routine clinical practice.
Published: 2019

20. In situ BCL2 expression is an independent prognostic factor in HIV-associated DLBCL, a LYMPHOVIR cohort study

Author: François Boué, Claire Delattre, Bruno Petitjean, Catherine Chassagne-Clément, Frédérique Capron, Rémi Lancar, Thierry Lazure, Laure Philippe, Sophie Prevot, Isabelle Goubin-Versini, Marie Parrens, Anrs-Co Lymphovir Cohort, Michele Algarte-Genin, Laure Gibault, Camille Laurent, Frédéric Charlotte, Caroline Besson, Nicolas Mounier, Régis Costello, Marie Pierre Chenard, Bettina Fabiani, Dominique Costagliola, Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier René Dubos [Pontoise], Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital l'Archet, Assistance Publique-Hôpitaux de Marseille (AP-HM), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles (CHV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance Publique - Hôpitaux de Marseille (APHM), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Cell of origin, [SDV]Life Sciences [q-bio], diffuse large B-cell lymphoma, HIV Infections, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, neoplasms, Cyclophosphamide, business.industry, HIV, Hematology, Middle Aged, medicine.disease, non-Hodgkin’s lymphoma, 3. Good health, Lymphoma, Non-Hodgkin's lymphoma, Gene Expression Regulation, Neoplastic, Survival Rate, Proto-Oncogene Proteins c-bcl-2, Doxorubicin, Vincristine, 030220 oncology & carcinogenesis, Cohort, HIV-1, Immunohistochemistry, Prednisone, Female, Lymphoma, Large B-Cell, Diffuse, Viral hepatitis, business, Rituximab, Diffuse large B-cell lymphoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Cohort study, BCL2 expression
Abstract: International audience; The prognostic value of cell of origin (COO) classification and BCL2 expression is not well established in diffuse large B-cell lymphoma (DLBCL) patients with human immunodeficiency virus (HIV) infection in the recent era. Phenotypic patterns were determined by immunohistochemistry (IHC) of pathological samples from patients with HIV-associated DLBCL prospectively enrolled in the French AIDS and Viral Hepatitis CO16 Lymphovir cohort between 2008 and 2015. Molecular subgroup classification into germinal centre B-cell (GCB) and non-GCB subtypes was determined using the Hans algorithm. Among 52 samples of systemic DLBCL subjected to centralized pathological analysis, 25 of the 42 tested for BCL2 expression were positive. Samples were further classified into GCB (n = 19) and non-GCB (n = 16) subtypes and 17 remained unclassified. In multivariable analysis, BCL2 expression was an independent pejorative prognostic biomarker [4-year progression-free survival (PFS): 52% for BCL2+ vs. 88% for BCL2- , P = 0·02] and tended to reduce 4-year overall survival (OS) (63% for BCL2+ vs. 88% for BCL2- , P = 0·06). The difference between CGB and non-GCB subtypes on PFS and OS did not reach significance (4-year PFS: 79% for GCB vs. 53% for non-GCB, P = 0·24 and 4-year OS: 78% for GCB vs. 69% for non-GCB, P = 0·34). BCL2 expression determined by IHC is an independent pejorative prognostic biomarker in HIV-associated DLBCL in the recent era. This supports the investigation of new therapeutic strategies in patients with BCL2 expression.
Published: 2019

21. National multicentric evaluation of quality of pathology reports for rectal cancer in France in 2016

Author: Anne Rullier, Céline Bazille, M. Desrousseaux, A. Daubech, Catherine Julie, F. Thélu, F. Le Pessot, B. Turlin, S. Stanislas, M.-S. Bordier, Armelle Bardier, C. Boutanos, Marie-Hélène Laverriere, R.-P. Eyremandi, A. Rousseau, T. Lazure, Janick Selves, Frédéric Bibeau, Nathalie Guedj, Magali Svrcek, M. Capdepont, Flora Poizat, B. Bonhomme, A. Demoures, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologie Nord Unilabs, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Pathologie [Rennes] = Pathology [Rennes], CHU Pontchaillou [Rennes], Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut Bergonié [Bordeaux], UNICANCER, CHU Grenoble, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Centre hospitalier de Pau, Département de Pathologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Libourne, Hopital de Périgueux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Routine practice, Pathology and Forensic Medicine, 03 medical and health sciences, Quality report, 0302 clinical medicine, Pathology report, medicine, Rectal Adenocarcinoma, Humans, Venous Invasion, Rectal cancer, Molecular Biology, Aged, Neoplasm Staging, Rectal Neoplasms, business.industry, Chemoradiotherapy, Cell Biology, General Medicine, Pathology Report, Middle Aged, medicine.disease, Neoadjuvant Therapy, 3. Good health, Radiation therapy, Treatment Outcome, 030104 developmental biology, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Concomitant, Neoadjuvant radiochemotherapy, Lymph Node Excision, Female, Radiotherapy, Adjuvant, France, Lymph Nodes, business
Abstract: International audience; The quality of pathologic assessment of rectal cancer specimens is crucial for treatment efficiency and survival. The Royal College of Pathologists (RCP) recommends evaluating the quality of the pathology report in routine practice using three quality indicators (QIs): the number of lymph nodes (LNs) analyzed (≥ 12), the rate of venous invasion (VI ≥ 30%), and peritoneal involvement (pT4a ≥ 10%). In this study, we evaluated the three QIs of the French national pathology reports and compared them with British guidelines and assessed the influence of neoadjuvant radiochemotherapy on QIs. From January 1 to December 31, 2016, all pathology reports for rectal adenocarcinoma were collected from French departments. Neoadjuvant radiochemotherapy included long-course radiotherapy with concomitant 5-FU-based chemotherapy. A total of 983 rectal cancer pathology reports were evaluated. A median of 15 LNs were analyzed and 81% of centers had ≥ 12 LNs. The rate of VI was 30% and 41% of centers had ≥ 30% VI. The rate of pT4a was 4% and 18% of centers reported ≥ 10% pT4a. None of the centers reached the threshold for the three QIs. All three QIs were lower after radiochemotherapy compared to surgery alone. In conclusion, in French routine practice, the values of two of the three QIs (LNs analyzed and VI) were globally in line with RCP guidelines. However, the rate of pT4a was very low, particularly after radiochemotherapy, suggesting its low value in rectal cancer.
Published: 2019

22. Highly sensitive methods are required to detect mutations in histiocytoses

Author: Quentin Riller, Valérie Taly, Sylvie Fraitag, Fleur Cohen-Aubart, Jean-François Emile, Zofia Hélias-Rodzewicz, Jean Donadieu, Marie Christine Copin, Zahir Amoura, T. Chazal, Marianne Kambouchner, Julien Haroche, Sarah Melloul, Sébastien Héritier, Nathalie Terrones, Anne Moreau, Frédéric Charlotte, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de pathologie [CHU Pitié-Salpêtrière], Université Paris Descartes - Paris 5 (UPD5), Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Anatomo-cyto-pathologie [Hôtel-Dieu, Nantes], Hôtel-Dieu de Nantes, Service de Pathologie [Hôpital Avicenne - APHP], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), SM received a fellowship from the Fondation pour la Recherche Médicale (FRM DEA20170637843). The study was supported by grants from the Association pour la Recherche et l'Enseignement en Pathologie (AREP)., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and TALY, Valerie
Subjects: [SDV]Life Sciences [q-bio], DNA Mutational Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Medicine, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Online Only Articles, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Reproducibility of Results, Hematology, Highly sensitive, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Histiocytoses, Mutation, Mutation (genetic algorithm), Cancer research, business, Histiocytosis, Biomarkers
Abstract: International audience
Published: 2019

23. Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma

Author: Bernd Wullich, Eva Comperat, Markus Eckstein, Yves Allory, Florian Haller, Nadine T. Gaisa, Bastian Keck, Abbas Agaimy, Evgeny A. Moskalev, Arndt Hartmann, Aurel Perren, Robert Stoehr, Ulrike Zinnall, Veronika Weyerer, Simone Bertz, Glen Kristiansen, Rebecca Weisser, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, RWTH Aachen University, Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), University of Bern, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University Hospital Bonn, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, Histology, [SDV.CAN]Life Sciences [q-bio]/Cancer, 610 Medicine & health, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Pathology and Forensic Medicine, Cohort Studies, 03 medical and health sciences, target sequencing, 0302 clinical medicine, nested variant, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Biomarkers, Tumor, Humans, ddc:610, Gene, Telomerase, Carcinoma, Transitional Cell, Bladder cancer, biology, CD24, CD44, GATA3, Wnt signaling pathway, High-Throughput Nucleotide Sequencing, Janus Kinase 3, General Medicine, molecular subtype, medicine.disease, Immunohistochemistry, Subtyping, 3. Good health, 030104 developmental biology, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, Mutation, Cancer research, biology.protein, urothelial bladder cancer, 570 Life sciences, Female, Urothelium
Abstract: International audience; Aims: Nested variant of urothelial carcinoma (NVUC) is rare, and only a few small series exist. Molecular characteristics and the classifying marker profile as well as therapeutic targets of this specific variant are mostly unknown. The aim of this study was to characterise NVUC at the molecular level in one of the largest cohorts to date. In addition, we applied an immunohistochemical marker panel in order to define the molecular subtype.Methods and results: Sixty NVUC cases were collected from different departments. TERT promoter mutation analysis was carried out in all samples using SNaPshot analysis. Targeted sequencing of 48 cancer‐related genes by next‐generation sequencing (NGS) analysis was performed in a subset of 26 cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63, FOXA1, GATA3, CD24 and CK20 were used to elucidate the molecular subtype. A total of 62.5% of NVUC cases harboured a mutation of the TERT promoter. Additionally, TP53, JAK3 and CTNNB1 were among the most frequently mutated genes identified by NGS analysis. Subtyping revealed that all NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20.Conclusions: In summary, NVUC belong to the luminal molecular subtype. Moreover, a subset of NVUC seems to be characterised by mutations of the Wnt and inflammatory pathways, including JAK3 mutations, indicating a different biological background compared to conventional urothelial bladder cancer.
Published: 2019

24. MYD88 Somatic Mutation Is a Diagnostic Criterion in Primary Cutaneous Large B-Cell Lymphoma

Author: Vanessa Szablewski, François Le Gall, Anne de Muret, Jean-Philippe Merlio, Nicolas Ortonne, Agnès Carlotti, Maxime Battistella, David Cappellen, Marie Beylot-Barry, Béatrice Vergier, Audrey Gros, F. Franck, François Comoz, Anne Pham-Ledard, Sarah Menguy, Anne Croue, Brigitte Balme, Marie-Hélène Lorton, Laurence Lamant, Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Pathologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Département de Pathologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de biologie de la tumeur, CHU Bordeaux [Bordeaux], Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], and Jonchère, Laurent
Subjects: PCFCL, [SDV.CAN]Life Sciences [q-bio]/Cancer, Primary cutaneous B-cell lymphoma, Dermatology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biochemistry, primary cutaneous follicle center lymphoma, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, primary cutaneous B-cell lymphoma, PCBCL, B-cell lymphoma, Molecular Biology, ComputingMilieux_MISCELLANEOUS, primary cutaneous marginal zone lymphoma, GC, business.industry, Germinal center, Cell Biology, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, PCLBCL-LT, medicine.disease, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, germinal center, primary cutaneous large B-cell lymphoma-leg type, 030220 oncology & carcinogenesis, PCMZL, Immunology, Mutation (genetic algorithm), Cancer research, Myeloid Differentiation Factor 88, Primary cutaneous marginal zone lymphoma, Differential diagnosis, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; no abstract
Published: 2016

25. Role of routine computed tomography scan in the oncological follow up of patients treated by radical cystectomy for bladder cancer

Author: Romain Mathieu, Solène-Florence Kammerer-Jacquet, Karim Bensalah, Benoit Peyronnet, Brigitte Laguerre, Quentin Alimi, Andrea Manunta, Francois Guille, Nathalie Rioux-Leclercq, Gregory Verhoest, Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Pathologie [Rennes] = Pathology [Rennes], CHU Pontchaillou [Rennes], Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Service d'urologie [Rennes], CHU Pontchaillou [Rennes]-Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Service de Pathologie [CHU Rennes]
Subjects: medicine.medical_specialty, recurrence, Multivariate analysis, Urology, medicine.medical_treatment, 030232 urology & nephrology, Computed tomography, tomography, Cystectomy, survival, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Median follow-up, Statistical significance, medicine, Humans, follow up, Neoplasm Staging, Retrospective Studies, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Bladder cancer, medicine.diagnostic_test, business.industry, Retrospective cohort study, medicine.disease, 3. Good health, Surgery, Treatment Outcome, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, bladder cancer, Neoplasm Recurrence, Local, medicine.symptom, Tomography, X-Ray Computed, business, Follow-Up Studies
Abstract: International audience; Objectives: To assess the impact of a prolonged follow-up schedule using computed tomography scan on oncological outcomes after radical cystectomy for bladder cancer. Methods: A single-center retrospective study was carried out. All patients who underwent a radical cystectomy for bladder cancer between 1992 and 2012 were included. The protocol for postoperative oncological follow up included a thoracoabdominal computed tomography scan twice per year for 2 years and then annually for life. The patients with tumor recurrence were divided into two groups: asymptomatic recurrences and recurrences diagnosed because of symptoms. Cancer-specific survivals were estimated using the Kaplan–Meier method and compared with the log–rank test. Cox proportional hazards regression models were used to determine the predictive factors of cancer-specific survival. Results: Overall, 331 patients were included in this analysis, and, of them, 48.5% had a cancer recurrence after a median follow up of 52.6 months. A total of 30 of these recurrences were diagnosed at routine follow up among asymptomatic patients (18.8%). A total of 50% of recurrences occurred during the first 6 months and 75% during the first year. Just 10 of the recurrences (6.3%) appeared more than 3 years after radical cystectomy. The 5-year cancer-specific survival was higher in patients with asymptomatic recurrences (15.7% vs 32.1%), but this difference was not statistically significant (P = 0.10). On multivariate analysis, detection of asymptomatic recurrence reached statistical significance (HR 0.55; P = 0.04). Conclusion: Routine computed tomography scan surveillance after radical cystectomy for bladder cancer might provide a survival benefit. The risk of recurrence beyond 3 years seems to be low, and further studies are required to determine the role of routine computed tomography scan in the follow up beyond this timeframe. © 2016 The Japanese Urological Association
Published: 2016

26. MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib

Author: Patrick Brest, Pascal Barbry, Marius Ilie, Paul Hofman, Sandra Lassalle, Elodie Long, Frédérique Tissier, Joséphine Zangari, Philippe Vielh, Géraldine Lemaire, Imène Sarah Henaoui, Catherine Butori, Alexandra Popa, Olivier Blanck, Christelle Bonnetaud, Hélène Trouette, Nicolas Guevara, Olivier Bordone, Alexandre Bozec, Bernard Mari, Geneviève Belléannée, J.-L. Sadoul, José Santini, Isabelle Peyrottes, Bogdan Catargi, Véronique Hofman, Martine Patey, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut de la physique de la matière condensée (IPMC), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratory of Clinical and Experimental Pathology, Laboratoire d’anatomie et cytologie pathologique, Hôpital Robert Debré, CHU de Reims, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Department of Pathology, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Service d'Endocrinologie (NICE - Endocrino), Hôpital Pasteur [Nice] (CHU), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bayer Cropscience, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Infection bactérienne, inflammation, et carcinogenèse digestive, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Brest, Patrick
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Vesicular Transport Proteins, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Vandetanib, 0302 clinical medicine, Piperidines, RNA interference, medullary thyroid carcinoma, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, microRNA, treatment, Thyroid, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Immunohistochemistry, Female, RNA Interference, Research Paper, medicine.drug, Adult, vandetanib, microRNA-375, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Line, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biomarkers, Tumor, medicine, Humans, Gene silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Thyroid Neoplasms, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, Cell Proliferation, business.industry, Cell growth, Gene Expression Profiling, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Carcinoma, Neuroendocrine, Gene expression profiling, MicroRNAs, 030104 developmental biology, Quinazolines, Cancer research, business
Abstract: In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib. Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.
Published: 2016

27. Renal parenchyma impairment characterization in partial unilateral ureteral obstruction in mice with intravoxel incoherent motion-MRI

Author: Ulrich Blank, Michel Peuchmaur, Simon A. Lambert, Miguel Albuquerque, Marianne Alison, Maguelonne Pons, Liza Ali, Benjamin Leporq, Alaa El Ghoneimi, Marie-Laurence Poli Merol, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence Inflamex [Paris] (Faculté de Médecine Xavier Bichat), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (COMUE) (USPC), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), RMN et optique : De la mesure au biomarqueur, Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Chirurgie pédiatrique et urologie [Hôpital Robert Debré - APHP], Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (COMUE) (USPC), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Radiologie Pédiatrique [AP-HP Hôpital Robert-Debré], Université Paris Diderot - Paris 7 (UPD7)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologie [Hôpital Beaujon - APHP], Hôpital Beaujon [AP-HP], Service de Pathologie [Hôpital Robert Debré - APHP], Sorbonne Paris Cité-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Chirurgie Pédiatrique [Reims] (CHU de Reims - American Memorial Hospital (Hôpital des enfants)), Centre Hospitalier Universitaire de Reims (CHU Reims)-American Memorial Hospital (Hôpital des enfants) [Reims], Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, and Paris‐Diderot University, French National Research Agency, Investissements d'Avenir programme, Grant/Award Number: ANR‐11‐IDEX‐0005‐02, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX, Association des amis de l'American Memorial Hospital Reims France, Section Française d'Urologie Pédiatrique et de l'Adolescent (SFUPA), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Blank, Ulrich, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie pédiatrique (EA_3102), Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-IFR02, Immunopathologie rénale, récepteurs et inflammation, and Hôpital Robert Debré
Subjects: medicine.medical_specialty, kidney, 030232 urology & nephrology, Urology, Renal function, Scintigraphy, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 030218 nuclear medicine & medical imaging, Motion, 03 medical and health sciences, 0302 clinical medicine, hydronephrosis, Fibrosis, partial unilateral ureteral obstruction, Parenchyma, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, Radiology, Nuclear Medicine and imaging, Hydronephrosis, ComputingMilieux_MISCELLANEOUS, Spectroscopy, Intravoxel incoherent motion, intravoxel incoherent motion, Kidney, medicine.diagnostic_test, business.industry, diffusion, medicine.disease, Magnetic Resonance Imaging, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Mice, Inbred C57BL, Perfusion, medicine.anatomical_structure, Molecular Medicine, business, Ureteral Obstruction
Abstract: International audience; Ureteropelvic junction obstruction constitutes a major cause of progressive pediatric renal disease. The biological mechanisms underlying the renal response to obstruction can be investigated using a clinically relevant mouse model of partial unilateral ureteral obstruction (pUUO). Renal function and kidney morphology data can be evaluated using renal ultrasound, scintigraphy and uro-magnetic resonance imaging (uro-MRI), but these methods are poorly linked to histological change and not all are quantitative. Here, we propose to investigate pUUO for the first time using an intravoxel incoherent motion diffusion sequence. The aim of this study was to quantitatively characterize impairment of the kidney parenchyma in the pUUO model. This quantitative MRI method was able to assess the perfusion and microstructure of the kidney without requiring the injection of a contrast agent. The results suggest that a perfusion fraction (f) reduction is associated with a decrease in the volume of the renal parenchyma, which could be related to decreased renal vascularization. The latter may occur before impairment by fibrosis and the findings are in accordance with the literature using the UUO mice model and, more specifically, on pUUO. Further investigation is required before this technique can be made available for the diagnosis and management of children with antenatal hydronephrosis and to select the optimal timing of surgery if required.Copyright © 2017 John Wiley & Sons, Ltd.
Published: 2018

28. Clinicopathological description of 43 oncocytic adrenocortical tumors: importance of Ki-67 in histoprognostic evaluation

Author: Delphine Vezzosi, Abir Al Ghuzlan, Delphine Drui, Matthieu Wargny, Sébastien Aubert, Sarra Smati, Olivier Chabre, Laurence Amar, Claire Briet, François Pattou, Rossella Libé, Martine Patey, Bertrand Cariou, Frédérique Tissier, Karine Renaudin, Nathalie Sturm, Jérôme Bertherat, Magalie Haissaguerre, Peggy Pierre, Mathilde Sibony, Jean Christophe Lifante, Claudine Berthozat, Emmanuelle Leteurtre, Christine Do Cao, Eric Baudin, Eric Mirallié, Service de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d’anatomie et cytologie pathologique, Hôpital Robert Debré, CHU de Reims, Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Université Paris-Sorbonne (UP4), Service d'HYPERVASC [CHU HEGP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Endocrinologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence pour les Maladies Rares, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'endocrinologie-diabétologie-nutrition [CHU Grenoble-Alpes], Service d’endocrinologie, diabétologie et maladies métaboliques [CHRU LIlle], Département d'endocrinologie - Bordeaux 2, Université Bordeaux Segalen - Bordeaux 2, Service d'Endocrinologie (TOURS - Endocrino), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie (TOULOUSE - Endocrino), CHU Toulouse [Toulouse], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Chirurgie Générale et Endocrinienne [Lyon], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de chirurgie générale et endocrinienne, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie Digestive et Endocrinienne [Nantes], Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Service d'Endocrinologie [Nantes], Unité de recherche de l'institut du thorax (ITX-lab), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Pathology, Proliferation index, Adenoma, [SDV]Life Sciences [q-bio], Malignancy, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, Biomarkers, Tumor, Adenoma, Oxyphilic, Humans, Stage (cooking), Retrospective Studies, biology, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Adrenal Cortex Neoplasms, 3. Good health, 030104 developmental biology, Ki-67 Antigen, 030220 oncology & carcinogenesis, Ki-67, Cohort, biology.protein, Female, business
Abstract: International audience; Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin-Weiss-Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20-59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin-Weiss-Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors.
Published: 2018

29. Clinicopathologic Features of CIC-NUTM1 Sarcomas, a New Molecular Variant of the Family of CIC-fused Sarcomas

Author: Gaëlle Pierron, François Le Loarer, Louise Galmiche-Rolland, Jean Michel Coindre, Franck Tirode, Sarah Watson, A. Michot, Daniel Pissaloux, Dominique Ranchère-Vince, Catherine Godfraind, Antoine Italiano, Laetitia Mayeur, Alexandre Vasiljevic, Karen Silva, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Laboratory of Solid Tumors Genetics, Nice University Hospital, Service de chirurgie plastique et reconstructive, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Unité de Génétique Somatique, Institut Curie [Paris], Service de Pathologie, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Lyon, Institut Bergonié [Bordeaux], UNICANCER, Centre de recherche de l'Institut Curie [Paris], INSERM U1218 ACTION, Université de Bordeaux (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Curie, and Institut Bergonié - CRLCC Bordeaux
Subjects: Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Adolescent, Recombinant Fusion Proteins, Soft Tissue Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Exon, 0302 clinical medicine, DUX4, Humans, Medicine, Child, Lung, medicine.diagnostic_test, business.industry, Breakpoint, Nuclear Proteins, Soft tissue, Sarcoma, medicine.disease, Phenotype, Neoplasm Proteins, 3. Good health, Repressor Proteins, 030104 developmental biology, medicine.anatomical_structure, Child, Preschool, 030220 oncology & carcinogenesis, Female, Surgery, Anatomy, business, Fluorescence in situ hybridization
Abstract: International audience; CIC-fused sarcomas represent an emerging family of tumors, for long connected to the Ewing family group of tumors, but underlined by distinct CIC fusions with different partners. 3' Fusion partners include DUX4, FOXO4, and, as recently emphasized, NUTM1. In this study, we report the clinicopathologic and molecular features of a series of 6 CIC-NUTM1 sarcomas. Mean age at diagnosis was 6 years (2 to 27 y), and 4 patients were male individuals. Primary tumors were located in the central nervous system (n=3), paravertebral soft tissue and epidural spaces (n=1, each), and lung (n=1). Median overall survival was 17.5 months (7 to 37 mo), and all but one patient died of disease. All tumors displayed classic features of CIC-DUX4 sarcomas with round cell to epithelioid microscopic appearance. Most tumors expressed ETV4 and NUTM1 (n=5/6 and 6/6, respectively), whereas WT1cter was positive in only 2 cases. All tested tumors were positive for break-apart fluorescence in situ hybridization for CIC and NUTM1. Apart from CIC or NUTM1 genomic breakpoints, no other recurrent copy number alteration was seen on genomic profiles. Fusion transcripts were identified by RNA-sequencing on either formalin-fixed paraffin-embedded or frozen material. CIC and NUTM1 breakpoints were located between exons 16 and 20 and exons 2 and 5, respectively. Altogether, CIC-NUTM1 sarcomas represent a new molecular variant of CIC-fused sarcomas with a predilection for the central nervous system and younger pediatric population. Its phenotype may be confused with NUT carcinomas.
Published: 2018

30. Selective vulnerability of the primitive meningeal layer to prenatal Smo activation for skull base meningothelial meningioma formation

Author: Matthieu Peyre, Franck Bielle, Julien Boetto, Michel Kalamarides, Caroline Apra, Gestionnaire, Hal Sorbonne Université, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Cancer Research, Pyridines, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Meningothelial Meningioma, Biology, Sonidegib, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Mice, Meninges, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Meningeal Neoplasms, otorhinolaryngologic diseases, Animals, Hedgehog Proteins, Craniofacial, Sonic hedgehog, Molecular Biology, Skull Base, Biphenyl Compounds, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Embryonic stem cell, Smoothened Receptor, nervous system diseases, Skull, 030104 developmental biology, medicine.anatomical_structure, chemistry, Cancer research, biology.protein, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Smoothened, Meningioma, Signal Transduction
Abstract: International audience; Somatic activating mutations of smoothened (SMO), a component of the embryonic sonic hedgehog (SHH) signaling pathway, are found in 3-5% of grade I meningiomas, most of them corresponding to meningothelial meningiomas located at the anterior skull base. By generating different developmental stage-specific conditional activations in mice, we define a restricted developmental window during which conditional activation of Smo in Prostaglandin D2-synthase-positive mesoderm-derived meningeal layer of the skull base results in meningothelial meningioma formation. We show a selective vulnerability of the arachnoid from the skull base to Smo activation to initiate tumor development. This prenatal period and specific topography are correlated to the timing and location of SHH signaling involvement in the formation of craniofacial and meninges patterning, strongly corroborating the hypothesis of a developmental origin for Smo-activated meningiomas. Finally, we provide preclinical in vitro evidence of the efficacy of the SMO-inhibitor Sonidegib, supporting further preclinical and clinical evaluation of targeted treatment for refractory SMO-mutant meningiomas.
Published: 2018

31. Phenotypes and survival in Erdheim-Chester disease: Results from a 165-patient cohort

Author: Fabrice Carrat, Philippe Cluzel, Stéphane Barete, Ahmed Idbaih, Frédéric Charlotte, Valérie Taly, Julien Haroche, Zofia Hélias-Rodzewicz, Jean-François Emile, Fleur Cohen-Aubart, Jean Donadieu, Zahir Amoura, Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Sorbonne Université (SU), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [CHU Pitié-Salpêtrière], Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), TALY, Valerie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], and Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière]
Subjects: Oncology, Adult, Male, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Erdheim-Chester Disease, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Cohort Studies, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Survival analysis, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, Hematology, Middle Aged, medicine.disease, Prognosis, Phenotype, Survival Analysis, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Erdheim–Chester disease, Cohort, Mutation, Female, France, business, 030217 neurology & neurosurgery, Cohort study
Abstract: International audience
Published: 2017

32. Clinical and pathological significance of cutaneous manifestations in ANCA-associated vasculitides

Author: Claire Le Jeunne, Selim Aractingi, Benoit Terris, François Maurier, Guillaume Le Guenno, Luc Mouthon, Agnès Carlotti, Alice Bérezné, Jonathan London, Alexiane Dallot, Nicolas Froment, Olivier Aumaître, Benjamin Terrier, Laurent Antunes, L. Frumholtz, Sara Laurent-Roussel, Nicolas Dupin, Loïc Guillevin, Sylvie Fraitag, Jean Louis Kemeny, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de médecine interne, Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), CHU Clermont-Ferrand, Service de Pathologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [Aulnay-sous-Bois], Hôpital Robert Ballanger [Aulnay-sous-Bois], Service d'Anatomie Pathologique [CHU Clermont-Ferrand], Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et de cytologie pathologiques [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Service de Dermatologie [CHU Cochin], VELUX, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de médecine interne, hôpital Gabriel-Montpied, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Universitaire Estaing, CHU Estaing, CHU Cochin [AP-HP], Centre Hospitalier Universitaire Gabriel Montpied, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Livedo, Pathology, medicine.medical_specialty, Immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Xanthoma, Skin Diseases, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Recurrence, Edema, medicine, Humans, Immunology and Allergy, Clinical significance, Pathological, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Prognosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Purpura, Phenotype, medicine.symptom, business, Vasculitis, Pyoderma gangrenosum
Abstract: Objectives Cutaneous manifestations (CM) in ANCA-associated vasculitides (AAV) are frequent, but data on clinical significance and clinical-pathological correlations are lacking. Methods We conducted a multicenter, retrospective study including 1553 AAV patients. Clinical, biological and pathological features have been analyzed, and tissue samples from 46 biopsies were reviewed in a blind manner. Results CM were more frequent in EGPA (53.0%) and MPA (51.9%) than in GPA (36.7%). Lesions more frequently associated with GPA were oral ulcers (4.6% vs. 2.5% in EGPA and 0.3% in MPA), while pyoderma gangrenosum and palpebral xanthoma were specific to GPA. Lesions associated with MPA were segmentary edema (19.5% vs. 12.7% in EGPA and 4.3% in GPA) and livedo (12.4% vs. 0.5% and 2.6%, respectively), whereas those associated with EGPA were urticarial lesions (11.5% vs. 1.9% in GPA and 3.5% in MPA) and nodules (12,2% vs. 8.9% in GPA and 4.7% in MPA). In GPA, CM patients had more frequent vasculitis than granulomatous phenotype, and poorer relapse-free and overall survival. Pathological analysis showed vasculitis and/or granulomatous infiltrates in 87.5% of GPA, in 61.1% of EGPA and in all MPA. Vasculitis was more frequently observed in purpura and nodules, while granulomas were differently located and organized within vessels or interstitium according to the type of lesions. Conclusion Each AAV seemed to be associated with a peculiar pattern of cutaneous lesions. CM are associated with poorer prognosis in GPA. Clinical-pathological correlations showed no specific feature of each AAV, whereas granulomatous infiltrates differ according to the type of lesions.
Published: 2017

33. Molecular and clinical diversity in primary central nervous system lymphoma

Author: Hernández-Verdin, I., Kirasic, E., Wienand, K., Mokhtari, K., Eimer, S., Loiseau, H., Rousseau, A., Paillassa, J., Ahle, G., Lerintiu, F., Uro-Coste, E., Oberic, L., Figarella-Branger, D., Chinot, O., Gauchotte, G., Taillandier, L., Marolleau, J.-P., Polivka, M., Adam, C., Ursu, R., Schmitt, A., Barillot, N., Nichelli, L., Lozano-Sánchez, F., Ibañez-Juliá, M.-J., Peyre, M., Mathon, B., Abada, Y., Charlotte, F., Davi, F., Stewart, C., de Reyniès, A., Choquet, S., Soussain, C., Houillier, C., Chapuy, B., Hoang-Xuan, K., Alentorn, A., Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University Medical Center Göttingen (UMG), Freie Universität Berlin, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Hôpitaux Civils de Colmar, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Sorbonne Université (SU), Centre Hospitalier Saint Jean de Perpignan, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Curie - Saint Cloud (ICSC), DESSAIVRE, Louise, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Anatomie Pathologique [CHRU Nancy], and École pratique des hautes études (EPHE)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Oncology, tumor heterogeneity, Hematology, multi-omics, microenvironment, PCNSL, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity.To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data.Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue.The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.
Published: 2023

34. CD163-positive tumor-associated macrophages and CD8-positive cytotoxic lymphocytes are powerful diagnostic markers for the therapeutic stratification of osteosarcoma patients: An immunohistochemical analysis of the biopsies fromthe French OS2006 phase 3 trial

Author: Françoise Rédini, Marta Jimenez, Corinne Bouvier, Claire Illac, Laurence Brugieres, Véronique Minard, Béatrice Marie, Vincent Minville, Gonzague de Pinieux, François Gouin, Marie-cecile Ledeley, Julia Gilhodes, Thomas Filleron, Sophie Piperno-Neumann, Natacha Entz-Werle, Frédérique Larousserie, Eric Mascard, Anne Gomez-Brouchet, Jean-Marc Guinebretière, Sébastien Aubert, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité de Biostatistiques [Toulouse], Institut Claudius Regaud-Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pathologie [Institut Curie], Institut Curie [Paris], Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Pathologie [AP-HP Hôpital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Oncologie Pédiatrique [CHU Hautepierre, Strasbourg], Hôpital de Hautepierre [Strasbourg], Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Pathologie [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie orthopédique et traumatologie pédiatrique [CHU Necker ], CHU Necker - Enfants Malades [AP-HP], Département d'Orthopédie [CHU Hôtel Dieu, Nantes], Hôtel-Dieu de Nantes, UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d'Oncologie Médicale [Institut Curie, Paris], Funding were obtained from the French National Cancer Institute (INCa Novartis Chugai Ligue Nationale contre le Cancer Fédération Enfants et Santé Société Française des Cancers et Leucémies de l’enfant (SFC and the Association Etoile de Martin). The ancillary biological studies were approved by the Sarcoma Group of UNICANCER, the 'Groupe des Sarcomes Français-Groupe d’étude des Tumeurs Osseuses' (GSF-GETO), the SFCE and the InterSarc network., Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT)-Institut Claudius Regaud, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), maurice, sandrine, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Pathology, medicine.medical_treatment, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, cd163, lcsh:RC254-282, Metastasis, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, osteosarcoma, Immunology and Allergy, Medicine, Cytotoxic T cell, Original Research, Chemotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, CD68, cd8, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, macrophages, 030104 developmental biology, pd1/pdl-1 checkpoint, 030220 oncology & carcinogenesis, Immunohistochemistry, Osteosarcoma, business, lcsh:RC581-607, CD163, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The French phase 3 trial (OS 2006) testing zoledronic acid, an osteoclast inhibitor, with chemotherapy and surgery did not improve the outcome of patients with osteosarcoma (OS). To understand this unexpected result, the presence of infiltrating immune cells was investigated in 124 pre-therapeutic biopsies of patients enrolled in the trial. The percentage of CD68/CD163 tumor-infiltrating macrophages (TAMs), CD8+ lymphocytes, osteoclasts, and the PD1/PDL-1 checkpoint were assessed by immunohistochemistry. M1/M2 macrophage polarization was characterized by pSTAT1/CMAF staining. The expression of these biomarkers was correlated with clinical outcome. No statistical correlations were found with response to chemotherapy. High CD163 levels (>50% of cells per core; 43.8% of patients) were associated with CMAF nuclear expression and significantly correlated with better overall survival (p = 0.0025) and longer metastasis progression-free survival (MPFS, p = 0.0315) independently of metastatic status (p = 0.002). Only a trend was observed for patients with high CD68-positive cells (p = 0.0582). CD8+ staining was positive in >50% of cases with a median staining of 1%. Lower CD8+ levels were associated with metastatic disease at diagnosis and the presence of CD8-positive cells significantly correlated with improved overall survival in zoledronate-treated patients (p = 0.0415). PD1/PDL-1 staining was negative in >80% of cases and was not correlated with outcome. Finally, CD163-positive TAMs and CD8 positive cells are crucial prognostic biomarkers in OS, whereas PD1/PDL-1 checkpoint plays a minor role. For the first time, we described a correlation between CD8 positive cells and survival in zoledronate-treated patients. The immunohistochemical analysis of the microenvironment in biopsies may represent a novel tool for therapeutic stratification.
Published: 2017

35. Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease-free survival in microsatellite stable colon cancer

Author: Sefrioui , France, Vermeulin , France, Blanchard , France, Chapusot , Caroline, Beaussire , Ludivine, Armengol-Debeir , Laura, Sesboué , Richard, Gangloff , Alice, Hebbar , Mohamed, Copin , Marie-Christine, Houivet , Estelle, Schwarz , Lilian, Clatot , Florian, Tuech , Jacques, Bénichou , Jacques, Martin , Laurent, Bouvier , Anne-Marie, Sabourin , Jean-Christophe, Sarafan-Vasseur , Nasrin, Frébourg , Thierry, Lepage , Côme, Michel , Pierre, Di Fiore , Frédéric, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Hôpital Charles Nicolle [Tunis], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pathologie, PRES Université Lille Nord de France-Faculté de Médecine Henri Warembourg-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Charles Nicolle [Rouen], Groupe d'étude des proliférations lymphoïdes (GPL), Unité de biostatistiques [CHU Rouen], Centre Guillaume le Conquérant, Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [Rouen], Normandie Université ( NU ) -Normandie Université ( NU ) -Hôpital Charles Nicolle [Rouen]-CHU Rouen, Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de pathologie [CHU Lille], Département de chirurgie [Rouen], CRLCC Henri Becquerel, Service de chirurgie digestive [Rouen], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Oncologie Médicale, and Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel )
Subjects: Male, Proto-Oncogene Proteins B-raf, MESH: Colon Cancer, DNA Copy Number Variations, Receptor, ErbB-2, MESH: Chromosomal instability, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, MESH: Copy Number Variation, Loss of Heterozygosity, Receptors, Cell Surface, Polymerase Chain Reaction, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Humans, Prospective Studies, Neoplasm Metastasis, Aged, Proportional Hazards Models, Colon Cancer, Tumor Suppressor Proteins, Carcinoma, Middle Aged, DCC Receptor, Prognosis, Copy Number Variation, Chromosomal instability, Microstellite Stable, Phenotype, Treatment Outcome, Colonic Neoplasms, MESH: Disease-Free Survival, Female, MESH: Microstellite Stable, Neoplasm Recurrence, Local, Microsatellite Repeats
Abstract: IF 5.531; International audience; We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% stage II patients vs 31% stage III patients (p
Published: 2017

36. Ductal adenocarcinoma of the prostate: Clinical and biological profiles

Author: Gaëlle Fromont, Laurent Salomon, Patrick Vourc'h, T. Charles, Morgan Rouprêt, Alexandre de la Taille, Idir Ouzaid, Eva Compérat, Jean-Baptiste Beauval, Franck Bruyère, Olivier Haillot, Laurence Choudat, Yves Allory, Nadine Houede, Armelle Vinceneux, Service d'Anatomopathologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université Francois Rabelais [Tours], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de pathologie [Mondor], Service d'urologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Anatomo-Pathologie [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Urologie - Transplantation Rénale - Andrologie, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP)
Subjects: Biochemical recurrence, Male, Pathology, medicine.medical_specialty, Urology, 030232 urology & nephrology, SPOP, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, medicine, Biomarkers, Tumor, PTEN, Humans, Stage (cooking), Aged, Neoplasm Staging, Retrospective Studies, Tissue microarray, ductal adenocarcinoma, biology, Prostatic Neoplasms, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, medicine.disease, prostate cancer, speckle-type POZ protein, 3. Good health, Carcinoma, Ductal, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, biology.protein, immunochemistry, Immunohistochemistry
Abstract: International audience; BACKGROUND:Ductal adenocarcinoma (DAC) is a rare and aggressive subtype of prostate cancer (PCa). In the present study, we analyzed the clinical and biological characteristics of DAC, in comparison with high grade conventional acinar PCa.METHODS:Samples and data were retrospectively collected from seven institutions and centrally reviewed. Immunohistochemistry was performed on tissue microarrays to assess the expression of candidate proteins, based on the molecular classification of PCa, including ERG, PTEN, and SPINK1. SPOP mutations were investigated from tumor DNA by Sanger sequencing. Relationships with outcome were analyzed using log-rank analysis and multivariable Cox regression.RESULTS:Among 56 reviewed prostatectomy specimens, 45 cases of DAC were finally confirmed. The pathological stage was pT3 in more than 66% of cases. ERG was expressed in 42% of DAC, SPINK1 in 9% (all ERG-negative), and two cases (ERG-negative) harbored a SPOP mutation. Compared to high grade conventional PCa matched for the pathological stage, cell proliferation was higher (P = 0.04) in DAC, and complete PTEN loss more frequent (P = 0.023). In multivariate analysis, SPINK1 overexpression (P = 0.017) and loss of PSA immunostaining (P = 0.02) were significantly associated with biochemical recurrence.CONCLUSION:these results suggest that, despite biological differences that highlighted DAC aggressiveness, the molecular classification recently proposed in conventional PCa could also be applied in DAC.
Published: 2017

37. Synchronous Metastatic Clear-Cell Renal Cell Carcinoma: A Distinct Morphologic, Immunohistochemical, and Molecular Phenotype

Author: Brigitte Laguerre, Romain Mathieu, Frédéric Dugay, Marc-Antoine Belaud-Rotureau, Julien Edeline, Julien Dagher, Gregory Verhoest, Guillaume Bouzillé, Sarah Medane, Jean Mosser, Benoit Peyronnet, Nathalie Rioux-Leclercq, Angélique Brunot, Solène-Florence Kammerer-Jacquet, Adélaïde Pladys, Alexandra Lespagnol, Karim Bensalah, Service de Pathologie [Rennes] = Pathology [Rennes], CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CRLCC Eugène Marquis (CRLCC), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Département d'oncologie médicale [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), The authors would like to acknowledge the Ligue Contre le Cancer, the CORECT, Rennes Hospital, and the French Institute of Cancer (INCa) for their financial aid.The authors would also like to thank the Center of Biological Resources of Rennes Hospital (BB-0033-00056, http://www.crbsante-rennes.com/) for managing patient samples as well as Pascale Bellaud and Roselyne Viel from the Histopathology platform H2P2-BIOSIT, Faculty of Medicine of Rennes for their technical support., Service de Pathologie [CHU Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CRLCC Eugène Marquis ( CRLCC ), École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service d'urologie, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nutrition, Métabolismes et Cancer ( NuMeCan ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1)
Subjects: Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, Oncology, Clear cell renal cell carcinoma, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Cell, Cell Cycle Proteins, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, B7-H1 Antigen, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Neoplasms, Multiple Primary, chemistry.chemical_compound, 0302 clinical medicine, Neoplasm Metastasis, Aged, 80 and over, Univariate analysis, Clinical outcome, Neoplasms, Second Primary, Middle Aged, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, Primary tumor, VEGF, Kidney Neoplasms, 3. Good health, Gene Expression Regulation, Neoplastic, Vascular endothelial growth factor, medicine.anatomical_structure, Von Hippel-Lindau Tumor Suppressor Protein, 030220 oncology & carcinogenesis, Cohort, Immunohistochemistry, Female, Adult, medicine.medical_specialty, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Diagnosis, Differential, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Carbonic Anhydrase IX, Carcinoma, Renal Cell, VHL gene, Adaptor Proteins, Signal Transducing, Aged, Retrospective Studies, business.industry, Genetic Variation, Membrane Proteins, Synchronous and metachronous metastases, medicine.disease, Survival Analysis, Sarcomatoid component, 030104 developmental biology, chemistry, business, Clear cell
Abstract: International audience; INTRODUCTION: Clear cell renal cell carcinomas (ccRCCs) are highly metastatic tumors with metastases detected at diagnosis (synchronous) or during follow-up (metachronous). To date, there have been no reports comparing primary ccRCC of patients with synchronous and metachronous metastases, who are different in terms of prognosis. Determining whether there is a phenotypic difference between these 2 groups could have important clinical implications. PATIENTS AND METHODS: In a retrospective consecutive cohort of 98 patients with ccRCC, 48 patients had metastases, including 28 synchronous and 20 metachronous presentations, with a follow-up of 10 years. For each primary tumor in these metastatic patients, pathologic criteria, expression of vascular endothelial growth factor, partitioning-defective 3, CAIX, and programmed death ligand 1 as detected by immunohistochemistry, and complete VHL status were analyzed. Univariate analysis was performed, and survival was assessed using Kaplan-Meier curves compared by log-rank test. RESULTS: Compared with primary ccRCC in patients with metachronous metastases, primary ccRCC in patients with synchronous metastases were significantly associated with a poorer Eastern Cooperative Oncology Group performance (P = .045), higher pT status (P = .038), non-inactivated VHL gene (P = .01), sarcomatoid component (P = .007), expression of partitioning-defective 3 (P = .007), and overexpressions of vascular endothelial growth factor (> 50%) (P = .017) and programmed death ligand 1 (P = .019). Patients with synchronous metastases had a worse cancer-specific survival than patients with metachronous metastases even from metastatic diagnosis (median survival, 16 months vs. 46 months, respectively; P = .01). CONCLUSION: This long-term study is the first to support the notion that synchronous m-ccRCC has a distinct phenotype. This is probably linked to the occurrence of oncogenic events that could explain the worse prognosis. These particular patients with metastases could benefit from specific therapy.
Published: 2017

38. DUSP5 and DUSP6, two ERK specific phosphatases, are markers of a higher MAPK signaling activation in BRAF mutated thyroid cancers

Author: Camille, Buffet, Karine, Hecale-Perlemoine, Léopoldine, Bricaire, Florent, Dumont, Camille, Baudry, Frédérique, Tissier, Jérôme, Bertherat, Beatrix, Cochand-Priollet, Marie-Laure, Raffin-Sanson, Françoise, Cormier, Lionel, Groussin, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de pathologie infectieuse CHU Cochin, Hôpital Ambroise Paré, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], HAL UPMC, Gestionnaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cell signaling, endocrine system diseases, lcsh:Medicine, Signal transduction, ERK signaling cascade, Biochemistry, Lung and Intrathoracic Tumors, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cell Movement, Thymic Tumors, Medicine and Health Sciences, Small interfering RNAs, Phosphorylation, Endocrine Tumors, lcsh:Science, Feedback, Physiological, Thyroid, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Signaling cascades, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Up-Regulation, Enzymes, Gene Expression Regulation, Neoplastic, Nucleic acids, Oncology, Thyroid Cancer, Papillary, Dual-Specificity Phosphatases, Anatomy, Research Article, Proto-Oncogene Proteins B-raf, Cell biology, MAPK signaling cascades, MAP Kinase Signaling System, Endocrine System, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transfection, Research and Analysis Methods, Carcinomas, [SDV.CAN] Life Sciences [q-bio]/Cancer, Dual Specificity Phosphatase 6, Cell Line, Tumor, Genetics, Animals, Humans, Point Mutation, Neoplasm Invasiveness, Thyroid Neoplasms, Non-coding RNA, Molecular Biology Techniques, Molecular Biology, Cell Proliferation, Biology and life sciences, Carcinoma, lcsh:R, Phosphatases, Cancers and Neoplasms, Proteins, Carcinoma, Papillary, Rats, Gene regulation, Mutation, Enzymology, RNA, lcsh:Q, Thyroid Carcinomas, Gene expression
Abstract: International audience; Background: Molecular alterations of the MAPK pathway are frequently observed in papillary thyroid carcinomas (PTCs). It leads to a constitutive activation of the signalling pathway through an increase in MEK and ERK phosphorylation. ERK is negatively feedback-regulated by Dual Specificity Phosphatases (DUSPs), especially two ERK-specific DUSPs, DUSP5 (nuclear) and DUSP6 (cytosolic). These negative MAPK regulators may play a role in thyroid carcinogenesis.Methods: MAPK pathway activation was analyzed in 11 human thyroid cancer cell lines. Both phosphatases were studied in three PCCL3 rat thyroid cell lines that express doxycycline inducible PTC oncogenes (RET/PTC3, H-RASV12 or BRAFV600E). Expression levels of DUSP5 and DUSP6 were quantified in 39 human PTCs. The functional role of DUSP5 and DUSP6 was investigated through their silencing in two human BRAFV600E carcinoma cell lines.Results: BRAFV600E human thyroid cancer cell lines expressed higher phospho-MEK levels but not higher phospho-ERK levels. DUSP5 and DUSP6 are specifically induced by the MEK-ERK pathway in the three PTC oncogenes inducible thyroid cell lines. This negative feedback loop explains the tight regulation of p-ERK levels. DUSP5 and DUSP6 mRNA are overexpressed in human PTCs, especially in BRAFV600E mutated PTCs. DUSP5 and/or DUSP6 siRNA inactivation did not affect proliferation in two BRAFV600E mutated cell lines, which may be explained by a compensatory increase in other phosphatases. In the light of this, we observed a marked DUSP6 upregulation upon DUSP5 inactivation. Despite this, DUSP5 and DUSP6 positively control cell migration and invasion.Conclusions: our results are in favor of a stronger activation of the MAPK pathway in BRAFV600E PTCs. DUSP5 and DUSP6 have pro-tumorigenic properties in two BRAFV600E PTC cell line models.
Published: 2017

39. Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy

Author: Karim Bensalah, Nathalie Rioux-Leclercq, Evanguelos Xylinas, Shahrokh F. Shariat, Michael Rink, Christopher G. Wood, Aurélie Mbeutcha, Romain Mathieu, Ilaria Lucca, Vitaly Margulis, Christian Seitz, Alberto Briganti, Harun Fajkovic, Mihai Dorin Vartolomei, Morgan Rouprêt, Jay D. Raman, Andrea Haitel, Pierre I. Karakiewicz, Jose A. Karam, Alon Z. Weizer, Dept of Urology [Vienne], Medizinische Universität Wien = Medical University of Vienna, Department of Cell and Molecular Biology, University of Medicine and Pharmacy, Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Dpt of Urology [Dallas], University of Texas Southwestern Medical Center [Dallas], Dpt of Urology [Houston], The University of Texas M.D. Anderson Cancer Center [Houston], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dept of Urology [Lausanne ], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Cancer Prognostics and Health Outcomes Unit, Université de Montréal (UdeM), Dpt of Urology [Michigan], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Urology - Penn State Milton S., S. Hershey Medical Center, Service de Pathologie [Rennes] = Pathology [Rennes], CHU Pontchaillou [Rennes], Dpt of Pathology [Vienna], Medical University of Vienna, Department of Pathology, Dpt of Urology [Hamburg], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Dpt of Urology [Milan], Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Service d'urologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dpt of Urology [New York], Weill Medical College of Cornell University [New York], Department of Urology, Comprehensive Cancer Center, General Hospital of Vienna, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vartolomei, Mihai Dorin, Mathieu, Romain, Margulis, Vitaly, Karam, Jose A., Rouprêt, Morgan, Lucca, Ilaria, Mbeutcha, Aurélie, Seitz, Christian, Karakiewicz, Pierre I., Fajkovic, Harun, Wood, Christopher G., Weizer, Alon Z., Raman, Jay D., Rioux-Leclercq, Nathalie, Haitel, Andrea, Bensalah, Karim, Rink, Michael, Briganti, Alberto, Xylinas, Evanguelo, Shariat, Shahrokh F., Service d'urologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service d'urologie et transplantation rénales [CHU Pitié-Salpêtrière], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service de Pathologie [CHU Rennes]
Subjects: Male, Recurrence Death, Neutrophils, Lymphovascular invasion, medicine.medical_treatment, 030232 urology & nephrology, Kaplan-Meier Estimate, Nephrectomy, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Leukocyte Count, 0302 clinical medicine, Retrospective Studie, Recurrence, Medicine, Lymphocytes, Multivariate Analysi, Neutrophil-to-lymphocyte ratio, Prognostic factor, Neutrophil, Kidney Neoplasm, Ureteral Neoplasm, Middle Aged, Prognosis, Kidney Neoplasms, Tumor Burden, 3. Good health, Death, 030220 oncology & carcinogenesis, Lymphocyte, Female, Original Article, Human, medicine.medical_specialty, Prognosi, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Carcinoma, Humans, Lymphocyte Count, Neutrophil to lymphocyte ratio, Ureteral neoplasm, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Carcinoma, Transitional Cell, Ureteral Neoplasms, business.industry, Proportional hazards model, fungi, Cancer, Retrospective cohort study, medicine.disease, Surgery, Multivariate Analysis, Proportional Hazards Model, Lymphadenectomy, Ureter, Urothelium, business
Abstract: International audience; Objective: Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort.Methods : Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models.Results: Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20–76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03).Conclusion:In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy.
Published: 2017

40. VLITL is a major cross-beta-sheet signal for fibrinogen A alpha-chain frameshift variants

Author: Ahmet Dogan, S. Valleix, Gilles Grateau, Nathalie Rioux-Leclercq, Franck Bridoux, Renan Goude, Jean Doucet, Cyrille Garnier, F. Briki, Philippe Derreumaux, Marc Delpech, Patrick Le Pogamp, Brigitte Nedelec, Laurent Martin, Caroline Beugnet, Mécanismes moléculaires dans les démences neurodégénératives ( MMDN ), École pratique des hautes études ( EPHE ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ), Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), CHU Pontchaillou [Rennes], Mayo Clinic [Rochester], Service de Pathologie [CHU Rennes], Génétique fonctionnelle, agronomie et santé ( GFAS ), Institut National de la Recherche Agronomique ( INRA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), CHU Necker - Enfants Malades [AP-HP], UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne ( UB ), CHU de Poitiers, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Laboratoire de biochimie théorique [Paris] ( LBT ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), l'Association Francaise contre l'Amylose, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Paris-Sud - Paris 11 (UP11), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [Rennes] = Pathology [Rennes], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bourgogne (UB), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, polypeptide, Protein Conformation, Amino Acid Motifs, Beta sheet, Peptide, genetic analysis, 030204 cardiovascular system & hematology, Kidney, Biochemistry, Renal amyloidosis, Thrombosis and Hemostasis, 0302 clinical medicine, Protein structure, Familial, genetic variability, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, genetics, Frameshift Mutation, Peptide sequence, chemistry.chemical_classification, fibrinogen Aalpha, Chemistry, fibril, Amyloidosis, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, VLITL peptide, Hematology, unclassified drug, fibrinogen A, priority journal, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], fibrinogen A alpha chain amyloidoisis, laser microdissection, Amyloidosis, Familial, kidney amyloidosis, Amyloid, in vitro study, beta sheet, Immunology, kidney biopsy, Fibril, Article, Frameshift mutation, protein aggregation, histology, in vivo study, 03 medical and health sciences, proteomics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], transmission electron microscopy, familial amyloidosis, medicine, Humans, human, Amino Acid Sequence, protein motif, liquid chromatography-mass spectrometry, Fibrinogen, Cell Biology, medicine.disease, human tissue, 030104 developmental biology, physiology, Protein Conformation, beta-Strand, pathology, beta-Strand, computer model
Abstract: International audience; The first case of hereditary fibrinogen A alpha-chain amyloidosis was recognized >20 years ago, but disease mechanisms still remain unknown. Here we report detailed clinical and proteomics studies of a French kindred with a novel amyloidogenic fibrinogen A alpha-chain frameshift variant, Phe521Leufs, causing a severe familial form of renal amyloidosis. Next, we focused our investigations to elucidate the molecular basis that render this A alpha-chain variant amyloidogenic. We show that a 49-mer peptide derived from the C-terminal part of the Phe521Leufs chain is deposited as fibrils in the patient's kidneys, establishing that only a small portion of Phe521Leufs directly contributes to amyloid formation in vivo. In silico analysis indicated that this 49-mer A alpha-chain peptide contained a motif (VLITL), with a high intrinsic propensity for beta-aggregation at residues 44 to 48 of human renal fibrils. To experimentally verify the amyloid propensity of VLITL, we generated synthetic Phe521Leufs-derived peptides and compared their capacity for fibril formation in vitro with that of their VLITL-deleted counterparts. We show that VLITL forms typical amyloid fibrils in vitro and is a major signal for cross-beta-sheet self-association of the 49-mer Phe521Leufs peptide identified in vivo, whereas its absence abrogates fibril formation. This study provides compelling evidence that VLITL confers amyloidogenic properties to A alpha-chain frameshift variants, yielding a previously unknown molecular basis for the pathogenesis of A alpha-chain amyloidosis.
Published: 2017

41. NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients

Author: Serge Leyvraz, Katrin S. Reiners, Christos Christidis, Jean-Yves Blay, Jonathan M. Pitt, Marion Lambert, Aurélien Marabelle, Frédéric Vély, Alexandre Ivagnes, Jean-François Emile, Christian Auclair, Benedita Rocha, Axel Le Cesne, Loic Chaigneau, Christelle Piperoglou, Kariman Chaba, Philippe Terrier, Eric Vivier, Nicolas Isambert, Julien Adam, Sylvie Rusakiewicz, Pierre Validire, Bruno Landi, Thierry Perniceni, Laurence Zitvogel, Sarah Jegou, Sylvie Bonvalot, Michaela Semeraro, Sophie Caillat-Zucman, David Enot, Sandrine Aspeslagh, Aurélie Perier, Christophe Borg, Vichnou Poirier-Colame, Anne Berger, Alexander M.M. Eggermont, Antoine Toubert, Niels Halama, Joachim Koch, Elke Pogge von Strandmann, Olivier Mir, Julien Domont, Anne Caignard, Jean-Michel Coindre, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Institut Gustave Roussy (IGR), Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Saclay, Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service d'Immunologie [AP-HM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Microorganismes, Molécules Bioactives et Physiopathologie Intestinale (LBM-E4), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] (DHU i2B ), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Departement d'Anatomopathologie, Institut Mutualiste de Montsouris (IMM), Hellenic Open University [Patras], Département de chirurgie digestive, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Jean-bernard, Département de biologie et pathologie médicales [Gustave Roussy], Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Service de Pathologie, Institut Bergonié, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et physiologie des lymphocytes T (U1020), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Virologie et Immunologie Moléculaires, Université Francois Rabelais [Tours], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'immunologie, AP-HP Hôpital universitaire Robert-Debré [Paris], Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Equipe 11, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de médecine oncologique [Gustave Roussy], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ), Université Paris-Sud 11 - Faculté de médecine ( UP11 UFR Médecine ), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] ( DITEP ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Microorganismes, Molécules Bioactives et Physiopathologie Intestinale ( LBM-E4 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] ( DHU i2B ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Institut Mutualiste de Montsouris ( IMM ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse ( U981 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Immunologie et Cancérologie Intégratives ( CRC - Inserm U1138 ), Centre de Recherche des Cordeliers ( CRC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ), Différenciation et physiologie des lymphocytes T ( U1020 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Necker Enfants-Malades ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Bergonié [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medical Centre of the Johannes Gutenberg University Mainz, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan), Medical Oncology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)
Subjects: 0301 basic medicine, medicine.medical_treatment, Immunology, PDGFRA, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, neoplasms, Original Research, Tumor microenvironment, GiST, business.industry, Cancer, medicine.disease, digestive system diseases, 3. Good health, Immunosurveillance, 030104 developmental biology, Imatinib mesylate, Oncology, 030220 oncology & carcinogenesis, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Tyrosine kinase
Abstract: International audience; Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST. Phenotypes based on disbalanced NKp30B/NKp30C ratio (Delta BClow) and low expression levels of NKp30A were identified in one third of patients with dismal prognosis across molecular subtypes. This Delta BClow blood phenotype was associated with a pro-inflammatory and immunosuppressive tumor microenvironment. In addition, detectable levels of the NKp30 ligand sB7-H6 predicted a worse prognosis in metastatic GIST. Soluble BAG6, an alternate ligand for NKp30 was associated with low NKp30 transcription and had additional predictive value in GIST patients with high NKp30 expression. Such GIST microenvironments could be rescued by therapy based on rIFN-alpha and anti-TRAIL mAb which reinstated innate immunity.
Published: 2017

42. APOL1 variants may induce HIV-associated nephropathy during HIV primary infection

Author: Gilbert Deray, Philippe Rouvier, Francis Barin, Roland Tubiana, Marine De Laroche, Geoffroy Desbuissons, Christine Katlama, Corinne Isnard Bagnis, Eric Caumes, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL-UPMC, Gestionnaire, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Microbiology (medical), 030232 urology & nephrology, Human immunodeficiency virus (HIV), medicine.disease_cause, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Pharmacology (medical), Pharmacology, HIV primary infection, business.industry, High mortality, Late complication, virus diseases, medicine.disease, Virology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Chronic infection, 030104 developmental biology, Infectious Diseases, African population, HIV-associated nephropathy, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business
Abstract: International audience; HIV-associated nephropathy (HIVAN) is still associated with high mortality, and is usually a late complication of HIV chronic infection. Since 2010, a link has been strongly established between APOL1 genetic variants and HIVAN, especially in the African population.
Published: 2017

43. Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study

Author: Andrea Haitel, Solene Jacquet-Kammerer, Stênio de Cássio Zequi, Mesut Remzi, Christopher G. Wood, Alexander Bachmann, Alon Z. Weizer, Shahrokh F. Shariat, Isabela Werneck da Cunha, Nathalie Rioux-Leclercq, Morgan Rouprêt, Jose A. Karam, Bernhard Grubmüller, Karim Bensalah, Michael Rink, Christian Seitz, Atessa Bahadori, Ricardo L. Favaretto, Romain Mathieu, Yair Lotan, Vitaly Margulis, Alberto Briganti, Jay D. Raman, Pierre I. Karakiewicz, Department of Urology [Sao Paulo], A. C. Camargo Hospital [São Paulo], Dpt of Urology and Comprehensive Cancer Center [Vienne], Medizinische Universität Wien = Medical University of Vienna, Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Dpt of Pathology [Vienna], Medical University of Vienna, Department of Pathology, Dpt of Urology [Dallas], University of Texas Southwestern Medical Center [Dallas], Dpt of Urology [Houston], The University of Texas M.D. Anderson Cancer Center [Houston], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'urologie et transplantation rénales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer Prognostics and Health Outcomes Unit, Université de Montréal (UdeM), Dpt of Urology [Michigan], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Urology - Penn State Milton S., S. Hershey Medical Center, Service de Pathologie [CHU Rennes], CHU Pontchaillou [Rennes], Dpt of Urology [Basel], University Hospital Basel [Basel], Dpt of Urology [Hamburg], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Dpt of Urology [Milan], Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Department of Urology, Weill Medical College of Cornell University [New York], Service de Neurologie [Rennes] = Neurology [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pathologie [Rennes] = Pathology [Rennes], Favaretto, Ricardo L., Bahadori, Atessa, Mathieu, Romain, Haitel, Andrea, Grubmüller, Bernhard, Margulis, Vitaly, Karam, Jose A., Rouprêt, Morgan, Seitz, Christian, Karakiewicz, Pierre I., Cunha, Isabela W., Zequi, Stenio C., Wood, Christopher G., Weizer, Alon Z., Raman, Jay D., Remzi, Mesut, Rioux-Leclercq, Nathalie, Jacquet-Kammerer, Solene, Bensalah, Karim, Lotan, Yair, Bachmann, Alexander, Rink, Michael, Briganti, Alberto, Shariat, Shahrokh F., Service d'Urologie [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Nephrology, Male, Survival, Lymphovascular invasion, 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Neoplasms, Multiple Primary, 0302 clinical medicine, Interquartile range, Retrospective Studie, Recurrence, Stage (cooking), Multivariate Analysi, medicine.diagnostic_test, Kidney Neoplasm, Lymph Node, Middle Aged, Ureteral Neoplasm, Cadherins, Prognosis, Immunohistochemistry, Kidney Neoplasms, 3. Good health, 030220 oncology & carcinogenesis, Original Article, Female, Carcinoma in Situ, Human, medicine.medical_specialty, Prognosi, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Antigens, CD, Internal medicine, Biopsy, medicine, Carcinoma, Humans, Retrospective Studies, Aged, Neoplasm Staging, Carcinoma, Transitional Cell, Ureteral Neoplasms, business.industry, Carcinoma in situ, E-cadherin, medicine.disease, Concomitant, Multivariate Analysis, Cadherin, Lymph Nodes, Neoplasm Grading, Urothelium, business, Prediction
Abstract: Purpose: To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. Methods: Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10Â % or more cells had decreased expression (
Published: 2017

44. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association

Author: Diane Damotte, Aspasia Stamatoullas, Herve Ghesquieres, Laurent Martin, Camille Laurent, Peggy Dartigues, Pierre Hirsch, Thierry Jo Molina, Clémentine Sarkozy, Anne-Sophie Michallet, Jehan Dupuis, Bettina Fabiani, Alexandra Traverse-Glehen, Gilles Salles, Franck Morsschauser, Marie Maerevoet, M. Parrens, Maria Gomes da Silva, Krimo Bouabdallah, Bertrand Coiffier, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Léon Bérard [Lyon], CHU Henri Mondor, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy ( IGR ), CRLCC Henri Becquerel, Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Instituto Português de Oncologia de Lisboa Francisco Gentil, Institut Jules Bordet, Departement de Pathologie, Institut Claudius Regaud,Toulouse, Fédération Nationale des Centres de Lutte contre le Cancer, Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, Hospices Civils de Lyon ( HCL ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor [Créteil], Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Gustave Roussy (IGR), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)
Subjects: Male, BEACOPP, Biopsy, medicine.medical_treatment, Gastroenterology, 0302 clinical medicine, Bone Marrow, Recurrence, immune system diseases, hemic and lymphatic diseases, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Articles, Hematology, Middle Aged, Prognosis, Combined Modality Therapy, Immunohistochemistry, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Disease Progression, Female, Rituximab, medicine.drug, Adult, medicine.medical_specialty, Lymphoma, B-Cell, Adolescent, Mediastinal Neoplasms, Gray zone lymphoma, Immunophenotyping, Young Adult, 03 medical and health sciences, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Biomarkers, Tumor, medicine, Humans, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, business.industry, medicine.disease, Survival Analysis, Surgery, Lymphoma, Radiation therapy, Regimen, ABVD, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies, 030215 immunology
Abstract: International audience; Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lym-phoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalat-ed BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.
Published: 2016

45. Development and validation of the Nancy histological index for UC

Author: Stefan Schreiber, Laurent Peyrin-Biroulet, Guillaume Cadiot, Virginie Cahn, Simon Travis, Silvio Danese, Aude Marchal-Bressenot, Walter Reinisch, Marie-Danièle Diebold, Claire Bastien, Julia Salleron, Camille Boulagnon-Rombi, Service de Pathologie [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de biostatistiques [ICL Alexis Vautrin], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Pathologie [Centre Hospitalier Sud Francilien], Centre Hospitalier Sud Francilien, CH Evry-Corbeil-CH Evry-Corbeil, Service d'hépato-gastroentérologie (CHU Reims), Gastroenterology [Istituto Clinico Humanitas], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Translational Gastroenterology Unit [Oxford University Hospitals], Oxford University Hospitals NHS Trust, University of Oxford [Oxford]-University of Oxford [Oxford], Service d'Hépato-gastro-entérologie [CHRU Nancy], Marchal-Bressenot, A, Salleron, J, Boulagnon-Rombi, C, Bastien, C, Cahn, V, Cadiot, G, Diebold, Md, Danese, S, Reinisch, W, Schreiber, S, Travis, S, and Peyrin-Biroulet, L
Subjects: medicine.medical_specialty, Pathology, Coefficient of determination, Index (economics), Colon, Intraclass correlation, Biopsy, [SDV]Life Sciences [q-bio], Severity of Illness Index, Correlation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Active disease, Linear regression, Severity of illness, medicine, Humans, Ulcerative Colitis, IBD CLINICAL, Observer Variation, medicine.diagnostic_test, business.industry, Gastroenterology, Reproducibility of Results, HISTOPATHOLOGY, PostScript, 030220 oncology & carcinogenesis, Linear Models, Colitis, Ulcerative, 030211 gastroenterology & hepatology, Mucosal Pathology, business, Algorithms
Abstract: Objective We developed a validated index for assessing histological disease activity in UC and established its responsiveness. Methods Two hundred biopsies were scored. The outcome was the Global Visual Evaluation (GVE). Eight histological features were tested. The Nancy index was developed by multiple linear regression and bootstrap process to create an index that best matched the GVE. Goodness of fit was assessed by the adjusted R squared (adjusted R-2). The second step was the validation of the index: 100 biopsies were scored for the Nancy index by three pathologists from different centres. Inter-reader reliability was evaluated for each reader. The relationship between the change of the Nancy index and the Geboes index was assessed to assess the responsiveness. Results After backward selection with bootstrap validation, 3/8 items were selected: ulceration (adjusted R-2=0.55), acute inflammatory infiltrate (adjusted R-2=0.88) and chronic inflammatory infiltrate (adjusted R-2=0.79). The Nancy index is defined by a 5-level classification ranging from grade 0 (absence of significant histological disease activity) to grade 4 (severely active disease). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.88 (95% CI 0.82 to 0.92) and the index had good interreader reliability (ICC=0.86 (0.81 to 0.99)). The correlation between the Nancy index and the Geboes score or the GVE was very good. The index had a good responsiveness with a high correlation between changes in the Geboes score and changes in the Nancy index (0.910 (0.813 to 0.955)). Conclusions A three descriptor histological index has been validated for use in clinical practice and clinical trials.
Published: 2016

46. Cisplatin and gemcitabine exert opposite effects on immunotherapy with PD-1 antibody in K-ras-driven cancer

Author: Christophe, Glorieux, Xiaojun, Xia, Xin, You, Zining, Wang, Yi, Han, Jing, Yang, Gauthier, Noppe, Christophe de, Meester, Jianhua, Ling, Annie, Robert, Hui, Zhang, Sheng-Ping, Li, Huamin, Wang, Paul J, Chiao, Li, Zhang, Xiaobing, Li, Peng, Huang, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/EPID - Pôle d'épidémiologie et biostatistique, and UCL - (SLuc) Service de pathologie cardiovasculaire
Subjects: Lung Neoplasms, Multidisciplinary, Programmed Cell Death 1 Receptor, Antineoplastic Agents, CD8-Positive T-Lymphocytes, Immunochemotherapy, Deoxycytidine, Gemcitabine, PD-1/PD-L1, B7-H1 Antigen, Proto-Oncogene Proteins p21(ras), Mice, Cell Line, Tumor, Animals, Humans, Immunologic Factors, Immunotherapy, Cisplatin, K-ras
Abstract: INTRODUCTION: Immunochemotherapy using PD-1/PD-L1 antibodies in combination with chemotherapeutic agents has become a mainstream treatment for cancer patients, but it remains unclear which drug combination would produce best therapeutic outcome. The purpose of this study is to compare two common chemotherapeutic drugs, gemcitabine and cisplatin, for their impact on the therapeutic efficacy of PD-1 antibody in K-ras-driven cancers known to overexpress PD-L1. METHODS: Both in vitro assays and syngeneic mouse tumor models were used in this study. Biochemical and molecular assays were used to determine the effects of drugs on T cell functions in cell culture models and mouse/human tumor tissues. Allograft tumor models with K-ras mutation were used to investigate the combination effect of gemcitabine or cisplatin with immunotherapy. Data of lung cancer patients with K-ras mutation treated with cisplatin and toripalimab were analyzed to evaluate the clinical relevance of the lab findings. RESULTS: Cisplatin and gemcitabine unexpectedly exert opposite effect on the therapeutic activity of PD-1 antibody in vivo . Gemcitabine antagonizes the therapeutic effect of PD-1 antibody due to its significant inhibition on CD8 + T cell infiltration, which was observed both in mouse tumor allografts and in human pancreatic cancer tissues. In contrast, cisplatin shows synergistic activity with PD-1 antibody by activation of CD8 + T cells through the DNA damage-mediated cGASSTING sensing mechanism, leading to increase of T cell infiltration and secretion of antitumor cytokines. Clinical data show that a combination of cisplatin with PD-1 antibody toripalimab could be effective in advanced lung cancer patients with K-ras mutation who failed prior therapies. CONCLUSIONS: Our study shows that a key factor in selecting chemotherapeutic agents for immunochemotherapy is the drug’s impact on T cell functions, and that cisplatinbased chemotherapy is an excellent choice for combination with immune checkpoint antibody to achieve favorable clinical outcome.
Published: 2022

47. Motion Estimation by Deep Learning in 2D Echocardiography: Synthetic Dataset and Validation

Author: Ewan Evain, Yunyun Sun, Khuram Faraz, Damien Garcia, Eric Saloux, Bernhard L. Gerber, Mathieu De Craene, Olivier Bernard, Bernard, Olivier, Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie Ultrasonore, Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Normandie Université (NU)-Normandie Université (NU), Université Catholique de Louvain = Catholic University of Louvain (UCL), MedisysResearch Lab (Medisys), Philips Research, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, and UCL - (SLuc) Service de pathologie cardiovasculaire
Subjects: Radiological and Ultrasound Technology, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Deep learning, [INFO.INFO-SD] Computer Science [cs]/Sound [cs.SD], [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Computer Science Applications, Motion, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Echocardiography, Ultrasound Imaging, [INFO.INFO-SD]Computer Science [cs]/Sound [cs.SD], Image Processing, Computer-Assisted, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Electrical and Electronic Engineering, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Motion Estimation, Software, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; Motion estimation in echocardiography plays an important role in the characterization of cardiac function, allowing the computation of myocardial deformation indices. However, there exist limitations in clinical practice, particularly with regard to the accuracy and robustness of measurements extracted from images. We therefore propose a novel deep learning solution for motion estimation in echocardiography. Our network corresponds to a modified version of PWC-Net which achieves high performance on ultrasound sequences. In parallel, we designed a novel simulation pipeline allowing the generation of a large amount of realistic B-mode sequences. These synthetic data, together with strategies during training and inference, were used to improve the performance of our deep learning solution, which achieved an average endpoint error of 0.07± 0.06 mm per frame and 1.20±0.67 mm between ED and ES on our simulated dataset. The performance of our method was further investigated on 30 patients from a publicly available clinical dataset acquired from a GE system. The method showed promise by achieving a mean absolute error of the global longitudinal strain of 2.5 ± 2.1% and a correlation of 0.77 compared to GLS derived from manual segmentation, much better than one of the most efficient methods in the state-of-the-art (namely the FFT-Xcorr block-matching method). We finally evaluated our method on an auxiliary dataset including 30 patients from another center and acquired with a different system. Comparable results were achieved, illustrating the ability of our method to maintain high performance regardless of the echocardiographic data processed.
Published: 2022

48. LSC17 score complements genetics and measurable residual disease in acute myeloid leukemia: an ALFA study

Author: Loic Vasseur, Laurène Fenwarth, Jérôme Lambert, Stéphane de Botton, Martin Figeac, Céline Villenet, Maël Heiblig, Pierre-yves Dumas, Christian Récher, Celine Berthon, Emilie Lemasle, Delphine Lebon, Juliette Lambert, Christine Terré, Karine Celli-Lebras, Hervé Dombret, Claude Preudhomme, Meyling H Cheok, Raphaël A. Itzykson, Nicolas Duployez, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Claude Huriez [Lille], CHU Lille, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Département de Génétique [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), and Service de pathologie [CHU Lille]
Subjects: [SDV]Life Sciences [q-bio], Hematology
Abstract: International audience; Whether the LSC17 gene expression can improve risk stratification in the context of NGS-based risk stratification and measurable residual disease (MRD) in AML patients treated intensively has not been explored. We analyzed LSC17 in 504 adult patients prospectively treated in the ALFA-0702 trial. Multiple (cyto)genetic alterations were associated with changes in LSC17, such as higher LSC17 in patients with RUNX1 or TP53 mutations, and lower scores in those with CEBPA and NPM1 mutations. LSC17-high patients had a lower rate of complete response (CR) or CR with incomplete platelet recovery (CRp) after one induction course in a multivariable analysis (OR=0.41, p=0.0007) accounting for European LeukemiaNet 2022 (ELN22) risk groups, age, and white blood cell (WBC) count. The LSC17-high status was associated with shorter overall survival (OS) (3-year OS: 70.0% versus 52.7% in LSC17-low patients, p
Published: 2023

49. UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia

Author: Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, Anaïs L’Haridon, Pierre Lemaire, Laurène Fenwarth, Sandrine Geffroy, Nathalie Helevaut, Karine Celli‑Lebras, Lionel Adès, Delphine Lebon, Céline Berthon, Alice Marceau-Renaut, Meyling Cheok, Juliette Lambert, Christian Récher, Emmanuel Raffoux, Jean-Baptiste Micol, Arnaud Pigneux, Claude Gardin, Eric Delabesse, Jean Soulier, Mathilde Hunault, Hervé Dombret, Raphael Itzykson, Emmanuelle Clappier, Claude Preudhomme, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'hématologie adulte [Hôpital de Saint Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Haut-Lévêque, and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Cancer Research, Oncology, Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults.
Published: 2023

50. Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Author: Dubois , Sydney, Viailly , J., Mareschal , Sylvain, Bohers , Elodie, Bertrand , P., Ruminy , Philippe, Maingonnat , Catherine, Jais , Jean-Philippe, Peyrouze , Pauline, Figeac , Martin, Molina , Thierry, Desmots , Fabienne, Fest , Thierry, Haioun , Corinne, Lamy , Thierry, Copie-Bergman , Christiane, Briere , J., Petrella , Tony, Canioni , Danielle, Fabiani , Bettina, Coiffier , Bertrand, Delarue , Richard, Peyrade , Frédéric, Bosly , A., Andre , M., Ketterer , Nicolas, Salles , Gilles, Tilly , Hervé, Leroy , Karen, Jardin , Fabrice, Viailly , Pierre-Julien, Bertrand , Bertrand, Brière , Josette, André , André, André , Marc, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche des Cordeliers - Equipe 20 'ingénierie des connaissances en santé', Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Service d'anatomie pathologique [CHU Necker], Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Maisonneuve-Rosemont, Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Dinant-Godinne UCL Namur, Department of Oncology, Lausanne Hospital, Lausanne Hospital, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National du Cancer (INCA), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, Rouen Business School, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Lille 2 - Faculté de Médecine, Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Université de Lille, Droit et Santé, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ), Unité de Taphonomie médico-légale ( UTML ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Microenvironnement et cancer ( MiCa ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de référence des mastocytoses, Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Côte d'Azur (UCA)-UNICANCER, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, Groupe d'étude des proliférations lymphoïdes, Université de Rouen - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC) - École pratique des hautes études (EPHE) - Université Paris Diderot - Paris 7 (UPD7) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL) - Université de Lille, Droit et Santé, Université de Rennes 1 (UR1) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Hôpital Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) - Groupe Hospitalier Saint-Louis-Lariboisière- Fernand-Widal - Université Paris Diderot - Paris 7 (UPD7), Centre de pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) - AP-HP Hôpital Necker - Enfants Malades [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC) - Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Saint-Antoine [APHP], Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - AP-HP Hôpital Necker - Enfants Malades [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Le Havre Normandie (ULH) - Université de Rouen - Institut National des Sciences Appliquées - Rouen (INSA Rouen), and Institut National des Sciences Appliquées (INSA) - Institut National des Sciences Appliquées (INSA)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, Receptors, Cytoplasmic and Nuclear, Cell Cycle Proteins, TUMOR-SUPPRESSOR GENE, Genome, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, PROGNOSTIC-SIGNIFICANCE, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Molecular Targeted Therapy, Prospective Studies, Precision Medicine, Exome sequencing, Genetics, Oncogene Proteins, B-Lymphocytes, High-Throughput Nucleotide Sequencing, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, 3. Good health, DNA-Binding Proteins, GENOME, Phosphotransferases (Alcohol Group Acceptor), Oncology, Vincristine, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Lymphoma, Large B-Cell, Diffuse, medicine.drug, EXPRESSION, [SDV.IMM] Life Sciences [q-bio]/Immunology, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, FREQUENT, Biology, Karyopherins, DNA sequencing, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, TARGETS, Exome Sequencing, medicine, Humans, RITUXIMAB, Cyclophosphamide, Tumor Necrosis Factor alpha-Induced Protein 3, Gene Expression Profiling, CLASSICAL HODGKIN LYMPHOMA, SOMATIC MUTATIONS, Precision medicine, medicine.disease, Lymphoma, Gene expression profiling, 030104 developmental biology, Doxorubicin, GTP-Binding Protein alpha Subunits, Gq-G11, Prednisone, BURKITT-LYMPHOMA, Diffuse large B-cell lymphoma
Abstract: Purpose: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials. Experimental Design: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients. The tumor DNA of 215 patients with CD20+de novo DLBCL in the prospective, multicenter, and randomized LNH-03B LYSA clinical trials was sequenced to deep, uniform coverage with the Lymphopanel. Cell-of-origin molecular classification was obtained through gene expression profiling with HGU133+2.0 Affymetrix GeneChip arrays. Results: The Lymphopanel was informative for 96% of patients. A clear depiction of DLBCL subtype molecular heterogeneity was uncovered with the Lymphopanel, confirming that activated B-cell–like (ABC), germinal center B-cell like (GCB), and primary mediastinal B-cell lymphoma (PMBL) are frequently affected by mutations in NF-κB, epigenetic, and JAK–STAT pathways, respectively. Novel truncating immunity pathway, ITPKB, MFHAS1, and XPO1 mutations were identified as highly enriched in PMBL. Notably, TNFAIP3 and GNA13 mutations in ABC patients treated with R-CHOP were associated with significantly less favorable prognoses. Conclusions: This study demonstrates the contribution of NGS with a consensus gene panel to personalized therapy in DLBCL, highlighting the molecular heterogeneity of subtypes and identifying somatic mutations with therapeutic and prognostic impact. Clin Cancer Res; 22(12); 2919–28. ©2016 AACR. See related commentary by Lim and Elenitoba-Johnson, p. 2829
Published: 2016

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