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7 results on '"MESH: Central Nervous System Neoplasms"'

1. Pediatric spinal pilocytic astrocytomas form a distinct epigenetic subclass from pilocytic astrocytomas of other locations and diffuse leptomeningeal glioneuronal tumours

Author

Alice Métais, Yassine Bouchoucha, Thomas Kergrohen, Volodia Dangouloff-Ros, Xavier Maynadier, Yassine Ajlil, Matthieu Carton, Wael Yacoub, Raphael Saffroy, Dominique Figarella-Branger, Emmanuelle Uro-Coste, Annick Sevely, Delphine Larrieu-Ciron, Maxime Faisant, Marie-Christine Machet, Ellen Wahler, Alexandre Roux, Sandro Benichi, Kevin Beccaria, Thomas Blauwblomme, Nathalie Boddaert, Fabrice Chrétien, François Doz, Christelle Dufour, Jacques Grill, Marie Anne Debily, Pascale Varlet, Arnault Tauziède-Espariat, Institut de neurophysiopathologie (INP), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Humans, [SDV]Life Sciences [q-bio], MESH: Child, Preschool, Intramedullary glioma, MESH: Retrospective Studies, [SDV.CAN]Life Sciences [q-bio]/Cancer, Methylation profiling, Diffuse leptomeningeal glioneuronal tumour, Glioneuronal tumour, MESH: Central Nervous System Neoplasms, Pathology and Forensic Medicine, MESH: Glioma, Cellular and Molecular Neuroscience, MESH: Astrocytoma, MESH: Child, MESH: Brain Neoplasms, Pilocytic astrocytoma, MESH: Epigenesis, Genetic, Neurology (clinical), Pediatric low-grade glioma
Abstract

Pediatric spinal low-grade glioma (LGG) and glioneuronal tumours are rare, accounting for less 2.8–5.2% of pediatric LGG. New tumour types frequently found in spinal location such as diffuse leptomeningeal glioneuronal tumours (DLGNT) have been added to the World Health Organization (WHO) classification of tumours of the central nervous system since 2016, but their distinction from others gliomas and particularly from pilocytic astrocytoma (PA) are poorly defined. Most large studies on this subject were published before the era of the molecular diagnosis and did not address the differential diagnosis between PAs and DLGNTs in this peculiar location. Our study retrospectively examined a cohort of 28 children with LGGs and glioneuronal intramedullary tumours using detailed radiological, clinico-pathological and molecular analysis. 25% of spinal PAs were reclassified as DLGNTs. PA and DLGNT are nearly indistinguishable in histopathology or neuroradiology. 83% of spinal DLGNTs presented first without leptomeningeal contrast enhancement. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that spinal PAs formed a unique methylation cluster distinct from reference midline and posterior fossa PAs, whereas spinal DLGNTs clustered with reference DLGNT cohort. FGFR1 alterations were found in 36% of spinal tumours and were restricted to PAs. Spinal PAs affected significantly younger patients (median age 2 years old) than DLGNTs (median age 8.2 years old). Progression-free survival was similar among the two groups. In this location, histopathology and radiology are of limited interest, but molecular data (methyloma, 1p and FGFR1 status) represent important tools differentiating these two mitogen-activated protein kinase (MAPK) altered tumour types, PA and DLGNT. Thus, these molecular alterations should systematically be explored in this type of tumour in a spinal location.

Published
2022
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2. The 2021 WHO classification of tumors of the central nervous system: A summary

Author

Andreas von Deimling, Arie Perry, Ho Keung Ng, David N. Louis, David W. Ellison, Dominique Figarella-Branger, Guido Reifenberger, Riccardo Soffietti, Cynthia Hawkins, Pieter Wesseling, Daniel J. Brat, Stefan M. Pfister, Ian A. Cree, Pathology, CCA - Imaging and biomarkers, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie Pathologique et de Neuropathologie [Hôpital de la Timone - CHU - APHM], and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)

Subjects
Central Nervous System, Cancer Research, diagnosis, WHO Classification Summary, [SDV]Life Sciences [q-bio], MESH: World Health Organization, MESH: Central Nervous System Neoplasms, Central Nervous System Neoplasms, 0302 clinical medicine, Pathology, Medicine, Pathology, Molecular, Cancer, 0303 health sciences, Brain, 3. Good health, medicine.anatomical_structure, Oncology, classification, 030220 oncology & carcinogenesis, brain tumor, Central nervous system, Oncology and Carcinogenesis, Brain tumor, World Health Organization, central nervous system, Humans, brian tumor, 03 medical and health sciences, MESH: Brain, Rare Diseases, Taxonomy (general), MESH: Central Nervous System, CNS TUMORS, Oncology & Carcinogenesis, Letters to the Editor, Grading (tumors), 030304 developmental biology, MESH: Pathology, Molecular, MESH: Humans, business.industry, Neurosciences, Molecular, medicine.disease, Brain Disorders, Brain Cancer, Neurology (clinical), Who classification, business, Neuroscience
Abstract

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

Published
2021
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3. The immune contexture of primary central nervous system diffuse large B cell lymphoma associates with patient survival and specific cell signaling

Author

Emmanuel Cornillot, Vanessa Lacheretz-Szablewski, Valérie Costes-Martineau, Valérie Rigau, Valère Cacheux, Melissa Alame, Jacques Colinge, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, and Hôpital Gui de Chauliac [CHU Montpellier]

Subjects
0301 basic medicine, MESH: Signal Transduction, Male, medicine.medical_treatment, Medicine (miscellaneous), Kaplan-Meier Estimate, MESH: Down-Regulation, MESH: Central Nervous System Neoplasms, Central Nervous System Neoplasms, Cohort Studies, 0302 clinical medicine, MESH: Aged, 80 and over, HLA Antigens, MESH: Tumor Microenvironment, Tumor Microenvironment, cellular interactions, Precision Medicine, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), MESH: Cohort Studies, MESH: HLA Antigens, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, immune contexture, Wnt signaling pathway, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, bioinformatics, Middle Aged, Prognosis, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, immunotherapy, Lymphoma, Large B-Cell, Diffuse, Research Paper, Signal Transduction, Adult, Notch signaling pathway, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, Human leukocyte antigen, Biology, MESH: Precision Medicine, MESH: Prognosis, 03 medical and health sciences, MESH: Gene Expression Profiling, Immune system, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, MESH: Kaplan-Meier Estimate, PCNSL, Aged, Tumor microenvironment, MESH: Humans, Gene Expression Profiling, MESH: Adult, Immunotherapy, medicine.disease, Immune checkpoint, MESH: Male, 030104 developmental biology, Cancer research, MESH: Lymphoma, Large B-Cell, Diffuse, Diffuse large B-cell lymphoma, MESH: Female
Abstract

International audience; Rationale: Primary central nervous system diffuse large B-cell lymphoma (PCNSL) is a rare and aggressive entity that resides in an immune-privileged site. The tumor microenvironment (TME) and the disruption of the immune surveillance influence lymphoma pathogenesis and immunotherapy resistance. Despite growing knowledge on heterogeneous therapeutic responses, no comprehensive description of the PCNSL TME is available. We hence investigated the immune subtypes of PCNSL and their association with molecular signaling and survival. Methods: Analysis of PCNSL transcriptomes (sequencing, n = 20; microarrays, n = 34). Integrated correlation analysis and signaling pathway topology enabled us to infer intercellular interactions. Immunohistopathology and digital imaging were used to validate bioinformatic results. Results: Transcriptomics revealed three immune subtypes: immune-rich, poor, and intermediate. The immune-rich subtype was associated to better survival and characterized by hyper-activation of STAT3 signaling and inflammatory signaling, e.g., IFNγ and TNF-α, resembling the hot subtype described in primary testicular lymphoma and solid cancer. WNT/β-catenin, HIPPO, and NOTCH signaling were hyper-activated in the immune-poor subtype. HLA down-modulation was clearly associated with a low or intermediate immune infiltration and the absence of T-cell activation. Moreover, HLA class I down-regulation was also correlated with worse survival with implications on immune-intermediate PCNSL that frequently feature reduced HLA expression. A ligand-receptor intercellular network revealed high expression of two immune checkpoints, i.e., CTLA-4/CD86 and TIM-3/LAGLS9. TIM-3 and galectin-9 proteins were clearly upregulated in PCNSL. Conclusion: Altogether, our study reveals that patient stratification according to immune subtypes, HLA status, and immune checkpoint molecule quantification should be considered prior to immune checkpoint inhibitor therapy. Moreover, TIM-3 protein should be considered an axis for future therapeutic development.

Published
2020
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4. Identification of novel recurrent ETV6-IgH fusions in primary central nervous system lymphoma

Author

Dominique Figarella-Branger, Franck Bielle, Clovis Adam, Louis Royer-Perron, Guillaume Gauchotte, David Meyronet, Aurélie Bruno, Chiara Villa, Amithys Rahimian, Blandine Boisselier, Carole Soussain, Fabrice Chrétien, Khê Hoang-Xuan, Caroline Houillier, Sandrine Eimer, Mailys Daniau, Frederic Davi, Karima Mokhtari, Karim Labreche, Justine Guegan, Pierre de la Grange, Agusti Alentorn, Marc Polivka, Audrey Rousseau, Frédéric Lemoine, 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), OncoNeuroTek [Paris], 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)-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], GenoSplice, Ltd, GenoSplice technology, GenoSplice [Paris], iCONICS, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomopathologie [Le Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hospices civils de Lyon, hôpital neurologique Pierre-Wertheimer, Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Pathologie [Hôpital Foch], Hôpital Foch [Suresnes], Centre Hospitalier Sainte Anne [Paris], Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Département de Pathologie Cellulaire et Tissulaire [CHU Angers] (Laboratoire d’Histopathologie-Cytopathologie), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital René HUGUENIN (Saint-Cloud), This work is part of the national program Cartes d’Identité des Tumeurs (CIT) funded and developed by the Ligue nationale contre le cancer, the Institut National du Cancer, Association pour la recherche sur les tumeurs cérébrales (ARTC), Cancéropôle Île-de-France 'Emergence 2015-1' (2015-1-EMERG-05-INSERM 6-1), Ligue nationale contre le cancer (Comité du Val d’Oise, R14044DD), Ligue Nationale contre le cancer 'Recherche épidemiologique' (N° PRE2015.LNCC), Fondation pour la Recherche Médicale (FDT20140930968), and the program 'Investissements d’avenir' ANR-10-IAIHU-06, and the Institut National du Cancer (INCa) (Réseau Expert National LOC, Lymphomes Oculo-Cérébraux). This study was supported by the Lymphomes Oculo-Cérébraux (LOC) study group network (Réseau national de centres experts des lymphomes primitifs du système nerveux central), We would like to thank the French LOC Network investigators. Specimens from Marseille were retrieved from the AP-HM tumor bank AC 2013-1786, ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), 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), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Incubateur et Pépinière d'Entreprises Paris-Salpêtrière (iPEPS-ICM), 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)-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)-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)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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 (SU)-Centre National de la Recherche Scientifique (CNRS), 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 (SU)-Centre National de la Recherche Scientifique (CNRS)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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)-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 neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, Cancer Research, Oncogene Proteins, Fusion, MESH: Central Nervous System Neoplasms, Fusion gene, Central Nervous System Neoplasms, 0302 clinical medicine, hemic and lymphatic diseases, MESH: Middle Aged, medicine.diagnostic_test, Primary central nervous system lymphoma, RNA sequencing, ETV6-IgH, MESH: Follow-Up Studies, Middle Aged, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Survival Rate, Oncology, fusion gene, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Female, Lymphoma, Large B-Cell, Diffuse, MESH: Biomarkers, Tumor, Haploinsufficiency, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, MESH: Proto-Oncogene Proteins c-ets, MESH: Survival Rate, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Prognosis, 03 medical and health sciences, primary CNS lymphoma, medicine, Biomarkers, Tumor, Humans, Survival rate, MESH: Humans, Proto-Oncogene Proteins c-ets, medicine.disease, MESH: Male, Lymphoma, haploinsufficiency, Repressor Proteins, ETV6, 030104 developmental biology, Cancer research, Immunoglobulin heavy chain, MESH: Lymphoma, Large B-Cell, Diffuse, Neurology (clinical), MESH: Female, Fluorescence in situ hybridization, Follow-Up Studies, MESH: Oncogene Proteins, Fusion
Abstract

International audience; Background: Primary central nervous system lymphoma (PCNSL) represents a particular entity within non-Hodgkin lymphomas and is associated with poor outcome. The present study addresses the potential clinical relevance of chimeric transcripts in PCNSL discovered by using RNA sequencing (RNA-seq).Methods: Seventy-two immunocompetent and newly diagnosed PCNSL cases were included in the present study. Among them, 6 were analyzed by RNA-seq to detect new potential fusion transcripts. We confirmed the results in the remaining 66 PCNSL. The gene fusion was validated by fluorescence in situ hybridization (FISH) using formalin-fixed paraffin-embedded (FFPE) samples. We assessed the biological and clinical impact of one new gene fusion.Results: We identified a novel recurrent gene fusion, E26 transformation-specific translocation variant 6-immunoglobulin heavy chain (ETV6-IgH). Overall, ETV6-IgH was found in 13 out of 72 PCNSL (18%). No fusion conserved an intact functional domain of ETV6, and ETV6 was significantly underexpressed at gene level, suggesting an ETV6 haploinsufficiency mechanism. The presence of the gene fusion was also validated by FISH in FFPE samples. Finally, PCNSL samples harboring ETV6-IgH showed a better prognosis in multivariate analysis, P = 0.03, hazard ratio = 0.33, 95% CI = 0.12-0.88. The overall survival at 5 years was 69% for PCNSL harboring ETV6-IgH versus 29% for samples without this gene fusion.Conclusions: ETV6-IgH is a new potential surrogate marker of PCNSL with favorable prognosis with ETV6 haploinsufficiency as a possible mechanism. The potential clinical impact of ETV6-IgH should be validated in larger prospective studies.

Published
2018
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5. Primary CNS lymphoma in children and adolescents: a descriptive analysis from the International Primary CNS Lymphoma Collaborative Group (IPCG)

Author

Oussama Abla, Sheila Weitzman, Michael Silver, Nancy D. Doolittle, Hervé Ghesquières, Jean-Yves Blay, Tracy T. Batchelor, Kamnesh R. Pradhan, Lauren E. Abrey, Rebecca A. Betensky, Michael F. Guerrera, Joachim M. Baehring, S. Eric Martin, Shafqat Shah, Edward A. Neuwelt, Brian P. O'Neill, The Hospital for sick children [Toronto] (SickKids), Equipe 11, 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)-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), University at Albany [SUNY], State University of New York (SUNY), Département Hématologie (FNCLCC), and Centre Léon Bérard [Lyon]

Subjects
Oncology, Male, Cancer Research, Lymphoma, medicine.medical_treatment, MESH: Central Nervous System Neoplasms, Central Nervous System Neoplasms, 0302 clinical medicine, MESH: Child, Antineoplastic Combined Chemotherapy Protocols, Young adult, Child, MESH: Treatment Outcome, Univariate analysis, Hazard ratio, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, MESH: Young Adult, 030220 oncology & carcinogenesis, Child, Preschool, Female, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Retrospective Studies, MESH: Adolescent, Chemotherapy, MESH: Humans, Performance status, business.industry, MESH: Child, Preschool, Cancer, Retrospective cohort study, MESH: Retrospective Studies, Odds ratio, medicine.disease, MESH: Male, Surgery, business, MESH: Lymphoma, MESH: Female, 030217 neurology & neurosurgery
Abstract

Purpose: To describe the demographic and clinical features and outcomes for children and adolescents with primary CNS lymphoma (PCNSL). Experimental Design: A retrospective series of children and adolescents with PCNSL was assembled from 10 cancer centers in 3 countries. Results: Twenty-nine patients with a median age of 14 years were identified. Sixteen (55%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or greater. Frontline therapy consisted of chemotherapy only in 20 patients (69%), while 9 (31%) had chemotherapy plus cranial radiotherapy. Most patients received methotrexate (MTX)-based regimens. Overall response rate was 86% (complete remission 69%, partial remission 17%). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 61% and 86%, respectively; the 3-year OS was 82%. Univariate analyses were conducted for age (≤14 vs. >14 years), PS (0 or 1 vs. >1), deep brain lesions, MTX dose, primary treatment with chemotherapy alone, intrathecal chemotherapy, and high-dose therapy. Primary treatment with chemotherapy alone was associated with better overall response rates with an odds ratio (OR) of 0.125 (P = 0.02). There was a marginally significant relationship between higher doses of MTX and response (OR = 1.5, P = 0.06). ECOG-PS of 0 to 1 was the only factor associated with better outcome with hazard ratios of 0.136 (P = 0.017) and 0.073 (P = 0.033) for PFS and OS, respectively. Conclusion: This is the largest series collected of pediatric PCNSL. The outcome of children and adolescents seems to be better than in adults. PS of 0 to 1 is associated with better survival. Clin Cancer Res; 17(2); 346–52. ©2011 AACR.

Published
2011
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6. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: the ESCALE study (SFCE)

Author

Dominique Plantaz, Didier Frappaz, Denis Hémon, Jacqueline Clavel, Brigitte Lacour, Xavier Rialland, Celine Icher, François Doz, Olivier Hartmann, Anne-Isabelle Bertozzi, Pascal Chastagner, Anne-Sophie Defaschelles, Matthieu Plichart, Alain Pierre-Kahn, Florence Menegaux, Secretariat, U754, Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Cancéropôle du Grand Est, Département de Pédiatrie, Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut Curie [Paris], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de médecine predictive et de recherche thérapeutique (IMPRT), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de pédiatrie, CHU Grenoble-Hôpital Michallon, Centre Robert Debré, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Registre National des Hémopathies malignes de l'Enfant (RNHE), Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants from INSERM, the Fondation de France, the Association pour la Recherche contre le Cancer (ARC), the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), the Agence Française de Sécurité Sanitaire de l'Environnement et du Travail (AFSSET) and the association 'Cent pour sang la vie'., Hôpital des Enfants, CHU Toulouse [Toulouse], Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Registre National des Tumeurs Solides de l'Enfant ( RNTSE ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Cancéropôle du Grand Est, Institut Gustave Roussy ( IGR ), Institut Curie, Hôpital des enfants, Institut de médecine predictive et de recherche thérapeutique ( IMPRT ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -CRLCC Oscar Lambret-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), CHU Angers, Registre National des Hémopathies malignes de l'Enfant ( RNHE ), and Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Pathology, MESH : Tea, MESH: Chi-Square Distribution, Physiology, MESH: Logistic Models, MESH : Central Nervous System Neoplasms, MESH: Risk Assessment, alcohols, MESH: Central Nervous System Neoplasms, Central Nervous System Neoplasms, 0302 clinical medicine, MESH: Pregnancy, MESH : Child, Pregnancy, Reference Values, MESH: Child, MESH: Incidence, Child, education.field_of_study, Incidence, MESH: Sex Distribution, MESH: Reference Values, MESH : Infant, MESH : Maternal Exposure, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, MESH: Infant, MESH: Case-Control Studies, MESH : Incidence, MESH : Paternal Exposure, 3. Good health, Oncology, risk factor, Maternal Exposure, Child, Preschool, 030220 oncology & carcinogenesis, Paternal Exposure, MESH : Case-Control Studies, medicine.medical_specialty, Alcohol Drinking, MESH: Probability, Risk Assessment, Article, MESH : Tobacco Smoke Pollution, 03 medical and health sciences, MESH : Adolescent, Humans, Risk factor, education, MESH: Age Distribution, Survival analysis, MESH: Adolescent, Chi-Square Distribution, MESH: Humans, MESH : Chi-Square Distribution, MESH : Humans, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Case-control study, Infant, MESH: Coffee, MESH : Follow-Up Studies, MESH: Adult, Odds ratio, medicine.disease, MESH : Coffee, Survival Analysis, MESH : Pregnancy, MESH : Alcohol Drinking, Logistic Models, Brain neoplasms, Case-Control Studies, Tobacco Smoke Pollution, MESH: Female, MESH: Alcohol Drinking, MESH : Logistic Models, Cancer Research, tea, MESH : Age Distribution, MESH : Child, Preschool, Epidemiology, MESH : Female, 030212 general & internal medicine, MESH : Risk Assessment, MESH: Maternal Exposure, MESH : Sex Distribution, Incidence (epidemiology), MESH: Tea, MESH : Adult, MESH: Survival Analysis, MESH: Tobacco Smoke Pollution, Female, epidemiology, France, Adult, Adolescent, MESH : Male, MESH : Probability, Population, coffee, MESH : Reference Values, smoking, Age Distribution, medicine, Sex Distribution, MESH : France, Probability, MESH: Paternal Exposure, business.industry, MESH: Male, MESH: France, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Survival Analysis, business, Follow-Up Studies
Abstract

International audience; Parental smoking and maternal alcohol and caffeinated beverage consumption are prevalent exposures which may play a role, either directly or through their influence on metabolism, in the aetiology of childhood malignant central nervous system (CNS) tumours. The hypothesis was investigated in the Epidemiological Study on childhood Cancer and Leukemia ESCALE study, a national population-based case-control study carried out in France in 2003-2004. The study included 209 incident cases of CNS tumours and 1681 population-based controls, frequency matched with the cases by age and sex. The data were collected through a standardized telephone interview of the biological mothers. No association between maternal smoking during pregnancy and CNS tumours [odds ratio (OR): 1.1 (0.8-1.6)] was observed. Paternal smoking during the year before birth was associated with CNS tumours (P for trend=0.04), particularly astrocytomas [OR: 3.1 (1.3-7.6)]. Maternal alcohol consumption during pregnancy was not associated with CNS tumours. Associations between ependymomas and the highest consumption of coffee [OR: 2.7 (0.9-8.1)] and tea [OR: 2.5 (1.1-5.9)] were observed. A strong association between CNS tumours and the highest maternal consumption of both coffee and tea during pregnancy was observed [OR: 4.4 (1.5-13)]. The results constitute additional evidence for a role of paternal smoking and suggest that maternal coffee and tea consumption during pregnancy may also increase the risk of CNS tumours. The study does not suggest an increased risk of CNS tumours related to alcohol consumption during pregnancy.

Published
2008
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7. Direct-tissue SELDI-TOF mass spectrometry analysis: a new application for clinical proteomics

Author

Jean-Paul Issartel, François Berger, David Ratel, Elisabeth Brambilla, Jessica Ternier, Alim-Louis Benabid, Ali Bouamrani, Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurochirurgie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, and Issartel, Jean-Paul

Subjects
Proteomics, Pathology, medicine.medical_specialty, Oligodendroglioma, Clinical Biochemistry, Mouse tissue, Mass spectrometry, Protein expression, MESH: Central Nervous System Neoplasms, Central Nervous System Neoplasms, Mice, 03 medical and health sciences, 0302 clinical medicine, Seldi tof, Biopsy, medicine, Animals, Humans, MESH: Animals, MESH: Mice, MESH: Oligodendroglioma, MESH: Organ Specificity, 030304 developmental biology, 0303 health sciences, MESH: Humans, medicine.diagnostic_test, Proteomic Profiling, Chemistry, MESH: Glioblastoma, MESH: Proteomics, Biochemistry (medical), MESH: Biological Markers, MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Organ Specificity, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, 030220 oncology & carcinogenesis, Glioblastoma, Biomarkers, Human cancer
Abstract

Background: New molecular profiling technologies can aid in analysis of small pathologic samples obtained by minimally invasive biopsy and may enable the discovery of key biomarkers synergistic with anatomopathologic analysis related to prognosis, therapeutic response, and innovative target validation. Thus proteomic analysis at the histologic level in healthy and pathologic settings is a major issue in the field of clinical proteomics. Methods: We used surface-enhanced laser desorption ionization-time-of-flight mass spectrometry (SELDI-TOF MS) technology with surface chromatographic subproteome enrichment and preservation of the spatial distribution of proteomic patterns to detect discrete modifications of protein expression. We performed in situ proteomic profiling of mouse tissue and samples of human cancer tissue, including brain and lung cancer. Results: This approach permitted the discrimination of glioblastomas from oligodendrogliomas and led to the identification of 3 potential markers. Conclusion: Direct tissue proteomic analysis is an original application of SELDI-TOF MS technology that can expand the use of clinical proteomics as a complement to the anatomopathological diagnosis.

Published
2006
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