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1. Adrenocortical carcinoma: Diagnosis, prognostic classification and treatment of localized and advanced disease

Author: Rossella Libé and Olivier Huillard
Subjects: Adrenocortical carcinoma, Diagnostic, Mitotane, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Adrenocortical carcinoma (ACC) is a rare cancer with an estimated incidence of 0.7 to 2.0 cases per 1 million population per year in the United States. It is an aggressive cancer originating in the cortex of the adrenal gland with a poor prognosis. The 5-year survival rate is less than 15% among patients with metastatic disease. In this article, we review the epidemiology and pathogenesis of ACC, the diagnostic procedures, the prognostic classification of ACC, and the treatment options from localized and resectable forms to advanced disease detailing recent therapeutic developments such as immunotherapy and molecularly targeted therapy.
Published: 2023
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2. Laparoscopic or Open Adrenalectomy for Stage I–II Adrenocortical Carcinoma: A Retrospective Study

Author: Martin Gaillard, Meva Razafinimanana, Alexandre Challine, Raphael L. C. Araujo, Rossella Libé, Mathilde Sibony, Maxime Barat, Jérôme Bertherat, Bertrand Dousset, David Fuks, and Sebastien Gaujoux
Subjects: adrenocortical carcinoma, adrenalectomy, laparoscopy, Medicine
Abstract: Surgical resection of adrenocortical carcinoma (ACC) is the only curative treatment. Even in localized (I–II) stages, open adrenalectomy (OA) is the gold standard, though laparoscopic adrenalectomy (LA) can be proposed in selected patients. Despite the postoperative benefits of LA, its role in the surgical management of patients with ACC remains controversial regarding oncologic outcomes. The aim of this retrospective study was to compare the outcomes of patients with localized ACC submitted to LA or OA in a referral center from 1995 to 2020. Among 180 consecutive patients operated on for ACC, 49 presented with localized ACC (19 LA and 30 OA). Baseline characteristics were similar between groups, except for tumor size. Kaplan-Meier estimates of 5-year overall survival were similar in both groups (p = 0.166) but 3-year disease-free survival was in favor of OA (p = 0.020). Though LA could be proposed in highly selected patients, OA should still be considered the standard approach in patients with known or suspected localized ACC.
Published: 2023
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3. Adrenal Mass Characterization in the Era of Quantitative Imaging: State of the Art

Author: Maxime Barat, Anne-Ségolène Cottereau, Sébastien Gaujoux, Florence Tenenbaum, Mathilde Sibony, Jérôme Bertherat, Rossella Libé, Martin Gaillard, Anne Jouinot, Guillaume Assié, Christine Hoeffel, Philippe Soyer, and Anthony Dohan
Subjects: adrenal glands, adrenal glands neoplasm, adrenal gland disease, tomography, X-rays computed, magnetic resonance imaging, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Detection and characterization of adrenal lesions have evolved during the past two decades. Although the role of imaging in adrenal lesions associated with hormonal secretion is usually straightforward, characterization of non-functioning adrenal lesions may be challenging to confidently identify those that need to be resected. Although many adrenal lesions can be readily diagnosed when they display typical imaging features, the diagnosis may be challenging for atypical lesions. Computed tomography (CT) remains the cornerstone of adrenal imaging, but other morphological or functional modalities can be used in combination to reach a diagnosis and avoid useless biopsy or surgery. Early- and delayed-phase contrast-enhanced CT images are essential for diagnosing lipid-poor adenoma. Ongoing studies are evaluating the capabilities of dual-energy CT to provide valid virtual non-contrast attenuation and iodine density measurements from contrast-enhanced examinations. Adrenal lesions with attenuation values between 10 and 30 Hounsfield units (HU) on unenhanced CT can be characterized by MRI when iodinated contrast material injection cannot be performed. 18F-FDG PET/CT helps differentiate between atypical benign and malignant adrenal lesions, with the adrenal-to-liver maximum standardized uptake value ratio being the most discriminative variable. Recent studies evaluating the capabilities of radiomics and artificial intelligence have shown encouraging results.
Published: 2022
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4. Preoperative Detection of Liver Involvement by Right-Sided Adrenocortical Carcinoma Using CT and MRI

Author: Alice Kedra, Anthony Dohan, Sébastien Gaujoux, Mathilde Sibony, Anne Jouinot, Guillaume Assié, Lionel Groussin Rouiller, Rossella Libé, Jérôme Bertherat, Philippe Soyer, and Maxime Barat
Subjects: adrenocortical carcinoma, liver, hepatectomy, neoplasm, staging, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: The major prognosis factor of adrenocortical carcinoma (ACC) is the completeness of surgery. The aim of our study was to identify preoperative imaging features associated with direct liver involvement (DLI) by right-sided ACC. Two radiologists, blinded to the outcome, independently reviewed preoperative CT and MRI examinations for eight signs of DLI, in patients operated for right-sided ACC and retrospectively included from November 2007 to January 2020. DLI was confirmed using surgical and histopathological findings. Kappa values were calculated. Univariable and multivariable analyses were performed by using a logistic regression model. Receiver operating characteristic (ROC) curves were built for CT and MRI. Twenty-nine patients were included. Seven patients had DLI requiring en bloc resection. At multivariable analysis, focal ACC bulge was the single independent sign associated with DLI on CT (OR: 60.00; 95% CI: 4.60–782.40; p < 0.001), and ACC contour disruption was the single independent sign associated with DLI on MRI (OR: 126.00; 95% CI: 6.82–2328.21; p < 0.001). Both signs were highly reproducible, with respective kappa values of 0.85 and 0.91. The areas under ROC curves of MRI and CT models were not different (p = 0.838). Focal ACC bulge on CT and ACC contour disruption on MRI are independent and highly reproducible signs, strongly associated with DLI by right-sided ACC on preoperative imaging. MRI does not improve the preoperative assessment of DLI by comparison with CT.
Published: 2021
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5. Positive Correlation Between 18F-FDG Uptake and Tumor-Proliferating Antigen Ki-67 Expression in Adrenocortical Carcinomas

Author: Rossella Libé, Aurore Pais, Florian Violon, Laurence Guignat, Fideline Bonnet, Olivier Huillard, Guillaume Assié, Martin Gaillard, Bertrand Dousset, Sébastien Gaujoux, Maxime Barat, Anthony Dohan, Mathilde Sibony, Jérôme Bertherat, Anne Segolene Cottereau, Florence Tenenbaum, Joël Coste, and Lionel Groussin
Subjects: Radiology, Nuclear Medicine and imaging, General Medicine
Published: 2023

6. Thyroid swellings in Renaissance illuminations

Author: Bertrand Lefrère, Rossella Libé, and Lionel Groussin
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, General Medicine
Published: 2023

7. Outcome of adrenocortical carcinoma patients included in early phase clinical trials: results from the French network ENDOCAN-COMETE

Author: Ségolène Hescot, Véronique Debien, Julien Hadoux, Delphine Drui, Magalie Haissaguerre, Christelle de la Fouchardiere, Delphine Vezzosi, Christine Do Cao, Rossella Libé, Christophe Le Tourneau, Eric Baudin, Christophe Massard, and Pauline du Rusquec
Subjects: Cancer Research, Oncology
Published: 2023

8. Recommandations conjointes du réseau National ENDOCAN-COMETE, de l’Association francophone de chirurgie endocrinienne et de la Société française d’urologie pour la prise en charge du carcinome corticosurrénalien

Author: Rossella Libé, Magalie Haissaguerre, Karine Renaudin, Matthieu Faron, Myriam Decaussin-Petrucci, Fréderic Deschamps, Anne-Paule Gimenez-Roqueplo, Eric Mirallie, Thibaut Murez, François Pattou, Laurence Rocher, David Taïeb, Pierre Henri Savoie, Antoine Tabarin, Jérôme Bertherat, Eric Baudin, and Christelle de la Fouchardière
Subjects: Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Published: 2023

9. Supplementary Tables S1-S2 from β-Catenin Activation Is Associated with Specific Clinical and Pathologic Characteristics and a Poor Outcome in Adrenocortical Carcinoma

Author: Frédérique Tissier, Jérôme Bertherat, Bruno Allolio, Xavier Bertagna, Bertrand Dousset, Marie-Cécile Vacher-Lavenu, Silviu Sbiera, Benedict Royer, Anne Audebourg, Ilham Chokri, Rossella Libé, Pierre Launay, Bruno Ragazzon, Martin Fassnacht, Sophie Grabar, and Sébastien Gaujoux
Abstract: Supplementary Tables S1-S2.
Published: 2023

10. Data from β-Catenin Activation Is Associated with Specific Clinical and Pathologic Characteristics and a Poor Outcome in Adrenocortical Carcinoma

Author: Frédérique Tissier, Jérôme Bertherat, Bruno Allolio, Xavier Bertagna, Bertrand Dousset, Marie-Cécile Vacher-Lavenu, Silviu Sbiera, Benedict Royer, Anne Audebourg, Ilham Chokri, Rossella Libé, Pierre Launay, Bruno Ragazzon, Martin Fassnacht, Sophie Grabar, and Sébastien Gaujoux
Abstract: Purpose: Activation of the Wnt/β-catenin signaling pathway is frequent in adrenocortical carcinoma (ACC) and might be associated with a more aggressive phenotype. The objective of this study was to assess the prognostic value of β-catenin immunohistochemistry and CTNNB1 (β-catenin gene)/APC (adenomatous polyposis coli gene) mutations in patients with resected primary ACC.Experimental design: In 79 patients with resected primary ACC from a French cohort (Cochin-COMETE), β-catenin expression was assessed on tumor specimens by immunohistochemistry. For patients with available DNA (n = 49), CTNNB1, and APC hotspot (mutation cluster region), were sequenced. Association between these results and the clinicopathologic characteristics of the ACC and overall and disease-free survival were studied. Results were confirmed on a tissue microarray from an independent multicentric cohort of 92 ACC from Germany (German-ENSAT cohort).Results: In the Cochin-COMETE cohort, the presence of a β-catenin nuclear staining was significantly associated with a higher ENSAT tumor stage (i.e., stages III and IV), higher Weiss score, more frequent necrosis, mitoses, and CTNNB1/APC mutations. β-Catenin nuclear staining and the presence of CTNNB1/APC mutations were both associated with decreased overall and disease-free survival, and were independent predictive factors of survival in multivariate analysis. The same results were observed in the German-ENSAT cohort.Conclusions: Wnt/β-catenin activation, confirmed by the presence of β-catenin nuclear staining, is an independent prognostic factor of overall and disease-free survival in patients with resected primary ACC. Clin Cancer Res; 17(2); 206–11. ©2010 AACR. Clin Cancer Res; 17(2); 328–36. ©2010 AACR.
Published: 2023

11. Supplementary Table 3 from Transcriptome Analysis Reveals that p53 and β-Catenin Alterations Occur in a Group of Aggressive Adrenocortical Cancers

Author: Jérôme Bertherat, Aurélien de Reyniès, Frédérique Tissier, Xavier Bertagna, Eric Clauser, Pierre Launay, Amato Fratticci, Guillaume Assié, Sébastien Gaujoux, Rossella Libé, and Bruno Ragazzon
Abstract: Supplementary Table 3 from Transcriptome Analysis Reveals that p53 and β-Catenin Alterations Occur in a Group of Aggressive Adrenocortical Cancers
Published: 2023

12. Supplementary Table 2 from Transcriptome Analysis Reveals that p53 and β-Catenin Alterations Occur in a Group of Aggressive Adrenocortical Cancers

Author: Jérôme Bertherat, Aurélien de Reyniès, Frédérique Tissier, Xavier Bertagna, Eric Clauser, Pierre Launay, Amato Fratticci, Guillaume Assié, Sébastien Gaujoux, Rossella Libé, and Bruno Ragazzon
Abstract: Supplementary Table 2 from Transcriptome Analysis Reveals that p53 and β-Catenin Alterations Occur in a Group of Aggressive Adrenocortical Cancers
Published: 2023

13. Supplementary Table 1 from Transcriptome Analysis Reveals that p53 and β-Catenin Alterations Occur in a Group of Aggressive Adrenocortical Cancers

Author: Jérôme Bertherat, Aurélien de Reyniès, Frédérique Tissier, Xavier Bertagna, Eric Clauser, Pierre Launay, Amato Fratticci, Guillaume Assié, Sébastien Gaujoux, Rossella Libé, and Bruno Ragazzon
Abstract: Supplementary Table 1 from Transcriptome Analysis Reveals that p53 and β-Catenin Alterations Occur in a Group of Aggressive Adrenocortical Cancers
Published: 2023

14. Identification of predictive criteria for pathogenic variants of primary bilateral macronodular adrenal hyperplasia (PBMAH) gene ARMC5 in 352 unselected patients

Author: Lucas Bouys, Anna Vaczlavik, Anne Jouinot, Patricia Vaduva, Stéphanie Espiard, Guillaume Assié, Rossella Libé, Karine Perlemoine, Bruno Ragazzon, Laurence Guignat, Lionel Groussin, Léopoldine Bricaire, Isadora Pontes Cavalcante, Fidéline Bonnet-Serrano, Hervé Lefebvre, Marie-Laure Raffin-Sanson, Nicolas Chevalier, Philippe Touraine, Christel Jublanc, Camille Vatier, Gérald Raverot, Magalie Haissaguerre, Luigi Maione, Matthias Kroiss, Martin Fassnacht, Sophie Christin-Maitre, Eric Pasmant, Françoise Borson-Chazot, Antoine Tabarin, Marie-Christine Vantyghem, Martin Reincke, Peter Kamenicky, Marie-Odile North, Jérôme Bertherat, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], CHU Lille, Recherche translationnelle sur le diabète - U 1190 (RTD), 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), CHU Rouen, Normandie Université (NU), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hospices Civils de Lyon (HCL), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), Physiologie et physiopathologie endocriniennes (PHYSENDO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), University Hospital of Würzburg, Klinikum der Universität [München], CHU Saint-Antoine [AP-HP], L B is recipient of research fellowships from the Cancer Research for Personalized Medicine (CARPEM) and the Fondation ARC pour la Recherche contre le Cancer, J B laboratory is supported by the Agence Nationale pour la Recherche grant ANR-18-CE14-0008-01 and the Fondation pour la Recherche Médicale (EQU201903007854). P T, C J, M F, S C M, F B C, M R, P C and J B clinical departments are part the European Reference Network on Rare Endocrine Conditions (Endo-ERN) – Project ID No 739572, and ANR-18-CE14-0008,STEROMICS,Steroïdogénomique de l'hypersécrétion des stéroïdes surrénaliens(2018)
Subjects: Armadillo Domain Proteins, Hyperplasia, Hydrocortisone, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 71 ARMC5, General Medicine, genetic screening, PBMAH, Endocrinology, Primary Bilateral Macronodular Adrenal Hyperplasia, adrenal tumors, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Adrenal Glands, Humans, Cushing syndrome, tumor suppressor gene, Retrospective Studies
Abstract: Objective Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a heterogeneous disease characterized by adrenal macronodules and variable levels of cortisol excess, with not clearly established clinical diagnostic criteria. It can be caused by ARMC5 germline pathogenic variants. In this study, we aimed to identify predictive criteria for ARMC5 variants. Methods We included 352 consecutive index patients from 12 European centers, sequenced for germline ARMC5 alteration. Clinical, biological and imaging data were collected retrospectively. Results 52 patients (14.8%) carried ARMC5 germline pathogenic variants and showed a more distinct phenotype than non-mutated patients for cortisol excess (24-h urinary free cortisol 2.32 vs 1.11-fold ULN, respectively, P < 0.001) and adrenal morphology (maximal adrenal diameter 104 vs 83 mm, respectively, P < 0.001) and were more often surgically or medically treated (67.9 vs 36.8%, respectively, P < 0.001). ARMC5-mutated patients showed a constant, bilateral adrenal involvement and at least a possible autonomous cortisol secretion (defined by a plasma cortisol after 1 mg dexamethasone suppression above 50 nmol/L), while these criteria were not systematic in WT patients (78.3%). The association of these two criteria holds a 100% sensitivity and a 100% negative predictive value for ARMC5 pathogenic variant. Conclusion We report the largest series of index patients investigated for ARMC5 and confirm that ARMC5 pathogenic variants are associated with a more severe phenotype in most cases. To minimize negative ARMC5 screening, genotyping should be limited to clear bilateral adrenal involvement and autonomous cortisol secretion, with an optimum sensitivity for routine clinical practice. These findings will also help to better define PBMAH diagnostic criteria.
Published: 2023

15. KDM1A inactivation causes hereditary food-dependent Cushing syndrome

Author: Lucas Bouys, Guillaume Assié, Anna Vaczlavik, Florian Violon, Constantine A. Stratakis, Eric Letouzé, Maria Candida Barisson Villares Fragoso, Patricia Vaduva, Jérôme Bertherat, Marie-Odile North, Mathilde Sibony, Stéphanie Espiard, Rossella Libé, Magalie Haissaguerre, Roberta Armignacco, Bertrand Dousset, Laurence Guignat, Karine Perlemoine, Lionel Groussin, Anne Jouinot, Annabel Berthon, Christopher Ribes, Bruno Ragazzon, Martin Reincke, Fidéline Bonnet, Gaetan Giannone, Eric Pasmant, Igor Tauveron, Philippe Emy, Isadora Pontes Cavalcante, Maxime Barat, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Pontchaillou [Rennes], CHU Lille, Centre Hospitalier Régional d'Orléans (CHRO), Université de Bordeaux (UB), CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, Universidade de São Paulo = University of São Paulo (USP), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, ANR-18-CE14-0008,STEROMICS,Steroïdogénomique de l'hypersécrétion des stéroïdes surrénaliens(2018), Admin, Oskar, and APPEL À PROJETS GÉNÉRIQUE 2018 - Steroïdogénomique de l'hypersécrétion des stéroïdes surrénaliens - - STEROMICS2018 - ANR-18-CE14-0008 - AAPG2018 - VALID
Subjects: medicine.medical_treatment, Adrenocortical tumors, ARMC5, Germline, Cushing syndrome, medicine, Humans, Allele, Cushing Syndrome, GIPR, Genetics (clinical), Exome sequencing, Armadillo Domain Proteins, Histone Demethylases, Hyperplasia, business.industry, Adrenalectomy, medicine.disease, Phenotype, KDM1A, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Macronodular Adrenal Hyperplasia, DNA methylation, Cancer research, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Ectopic expression, business
Abstract: International audience; PURPOSE: This study aimed to investigate the genetic cause of food-dependent Cushing syndrome (FDCS) observed in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) and adrenal ectopic expression of the glucose-dependent insulinotropic polypeptide receptor. Germline ARMC5 alterations have been reported in about 25% of PBMAH index cases but are absent in patients with FDCS. METHODS: A multiomics analysis of PBMAH tissues from 36 patients treated by adrenalectomy was performed (RNA sequencing, single-nucleotide variant array, methylome, miRNome, exome sequencing). RESULTS: The integrative analysis revealed 3 molecular groups with different clinical features, namely G1, comprising 16 patients with ARMC5 inactivating variants; G2, comprising 6 patients with FDCS with glucose-dependent insulinotropic polypeptide receptor ectopic expression; and G3, comprising 14 patients with a less severe phenotype. Exome sequencing revealed germline truncating variants of KDM1A in 5 G2 patients, constantly associated with a somatic loss of the KDM1A wild-type allele on 1p, leading to a loss of KDM1A expression both at messenger RNA and protein levels (P = 1.2 × 10(-12) and P < .01, respectively). Subsequently, KDM1A pathogenic variants were identified in 4 of 4 additional index cases with FDCS. CONCLUSION: KDM1A inactivation explains about 90% of FDCS PBMAH. Genetic screening for ARMC5 and KDM1A can now be offered for most PBMAH operated patients and their families, opening the way to earlier diagnosis and improved management.
Published: 2022

16. OR04-3 Genetic Alterations of ARMC5 and KDM1A Are Associated With Different Expression Profiles of Illegitimate Receptors in Primary Bilateral Macronodular Adrenal Hyperplasia

Author: Roberta Armignacco, Guillaume Assié, Maxime Barat, Jérôme Bertherat, Annabel Berthon, Fidéline Bonnet-Serrano, Isadora P Cavalcante, Bertrand Dousset, Gaëtan Giannone, Lionel Groussin, Laurence Guignat, Anne Jouinot, Rossella Libé, Marie-Odile North, Eric Pasmant, Karine Perlemoine, Bruno Ragazzon, Christopher Ribes, Mathilde Sibony, Anna Vaczlavik, Patricia Vaduva, Florian Violon, and Lucas Bouys
Subjects: Endocrinology, Diabetes and Metabolism
Abstract: Introduction Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a heterogeneous disease characterized by bilateral adrenal macronodules responsible for adrenal Cushing. To date, two genetic causes of PBMAH are known: germline inactivating variants of the tumor suppressor genes ARMC5 identified in 2013 (Assié, N Eng J Med 2013), responsible for 20 to 25% of index cases, and KDM1A, identified recently (Vaczlavik, GIM 2021; Chasseloup, Lancet D&E 2021), responsible for the rare presentation associated with food-dependent Cushing's syndrome (FDCS) due to aberrant expression of the GIP receptor (GIPR) in adrenocortical cells. Multiple other illegitimate receptors are known to be responsible for abnormal cortisol response to various physiological stimuli in PBMAH. A recent multiomic analysis, identified three distinct molecular PBMAH groups: G1 with ARMC5-mutated tumors, G2 with KDM1A-mutated tumors from FDCS patients, and G3 with no identified genetic cause at present. We aimed to identify specific expression profiles of illegitimate receptors in the three groups. Methods Based on the transcriptome data obtained by RNA sequencing (Illumina) of the tumors from 31 patients (G1/ARMC5, 16 patients; G2/KDM1A, 6 patients; G3, 9 patients), expression of the following genes, encoding potential illegitimate receptors, were compared: ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, AVPR1A, AVPR1B, AVPR2, GCGR, GIPR, HTR4, HTR7, LHCGR. Calculations were performed using R statistical software. The Bioconductor limma package was used to analyze mRNA differential expression. Results G1/ARMC5 tumors showed a relative overexpression of the vasopressin receptors AVPR1A and AVPR1B compared to the two other groups (fold-change [FC] =7.39, p Conclusion This study reveals specific expression profiles of illegitimate receptors related to the three molecular groups. ARMC5 tumors are associated with the overexpression of two vasopressin receptors, while, besides GIPR, KDM1A inactivation seems to drive the overexpression of the LH/hCG receptor, as previously suggested in patients with FDCS (Bertherat, JCE&M 2005), potentially responsible for Cushing's syndrome associated with pregnancy and menopause. These molecular patterns need to be corroborated by clinical data with a systematic testing of the aberrant cortisol responses. Additionally, further studies would be needed to investigate the clinical relevance and significance of moderate fold-changes in gene expression (e.g. Presentation: Saturday, June 11, 2022 12:00 p.m. - 12:15 p.m.
Published: 2022

17. Recurrence of a Pheochromocytoma With TNEM127 Mutation Negative on 18F-FDOPA and 18F-FDG but Positive on 123I-MIBG and 68Ga-DOTATOC Imaging

Author: Cyril Garcia, Rossella Libé, Bertrand Dousset, Anne-Ségolène Cottereau, and Florence Tenenbaum
Subjects: medicine.medical_specialty, Adrenal Gland Neoplasms, Pheochromocytoma, medicine.disease_cause, Scintigraphy, Octreotide, Metastasis, Iodine Radioisotopes, Germline mutation, Paraganglioma, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, medicine, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Aged, Mutation, medicine.diagnostic_test, 123i mibg, business.industry, General Medicine, medicine.disease, Dihydroxyphenylalanine, Functional imaging, 3-Iodobenzylguanidine, Female, Radiology, business
Abstract: We report the case of a 75-year-old woman with liver metastasis as a recurrence of a pheochromocytoma resected 10 years ago, with a rare germline mutation in transmembrane protein 127, falsely negative on 18F-FDOPA and 18F-FDG PET/CT scans but strongly positive on 123I-MIBG scintigraphy and on 68Ga-DOTATOC PET/CT. Functional imaging has a key role in diagnosis of pheochromocytoma and paraganglioma, especially 18F-FDOPA shows very high sensitivity and specificity. However, 18F-FDOPA might be falsely negative in some of these tumors, depending on specific mutations, and thus MIBG or 68Ga-DOTATOC imaging could be an alternative.
Published: 2021

18. Results of the ADIUVO trial, the first randomized study on post-operative adjuvant mitotane in patients with adrenocortical carcinoma

Author: Paola Loli, Isabelle Bourdeau, Irina Bancos, Hélène Lasolle, R Haak Harm, Matthias Kroiss, Soraya Puglisi, Alfredo Berruti, Paola Perotti, Wiebke Arlt, Anna Calabrese, Rossella Libé, Villares Fragoso Maria Candida Barisson, Paola Berchialla, Felix Beuschlein, Jérôme Bertherat, Tina Dušek, Massimo Terzolo, Bénédicte Decoudier, Darko Kastelan, Eric Baudin, Marcus Quinkler, André Lacroix, Martin Fassnacht, and Letizia Canu
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Urology, medicine.disease, law.invention, Randomized controlled trial, law, Medicine, Adrenocortical carcinoma, Mitotane, In patient, Post operative, business, Adjuvant, medicine.drug
Published: 2021

19. What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question

Author: Soraya Puglisi, Felix Megerle, Paola Perotti, Isabelle Bourdeau, Marcus Quinkler, Martin Fassnacht, Alfredo Berruti, Ulrich Dischinger, Barbara Altieri, Darko Kastelan, André Lacroix, Massimo Terzolo, Letizia Canu, Paola Loli, Eric Baudin, Rossella Libé, Paola Berchialla, Harm R. Haak, Anna Calabrese, Filippo Ceccato, Vittoria Basile, Felix Beuschlein, RS: CAPHRI - R1 - Ageing and Long-Term Care, Interne Geneeskunde, University of Zurich, and Puglisi, Soraya
Subjects: Oncology, Recurrence free sur-vival, mitotane, medicine.medical_specialty, recurrence, Treatment duration, medicine.medical_treatment, 10265 Clinic for Endocrinology and Diabetology, adjuvant treatment, lcsh:Medicine, Medicine (miscellaneous), 610 Medicine & health, 030209 endocrinology & metabolism, recurrence free survival, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, adrenocortical cancer, medicine, Retrospective analysis, timing, Adrenocortical carcinoma, In patient, Mitotane, ddc:610, Radical surgery, business.industry, lcsh:R, 2701 Medicine (miscellaneous), medicine.disease, Discontinuation, 030220 oncology & carcinogenesis, Adjuvant treatment, Adrenocortical cancer, Recurrence, Timing, business, Adjuvant, medicine.drug
Abstract: A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.
Published: 2021

20. Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma

Author: Jérôme Cartry, Sandra Sigala, Mouhammed Amir Habra, Mohamad Anas Sukkari, Alfredo Berruti, Richard A Feelders, Gherardo Mazziotti, Jérôme Bertherat, Eric Baudin, Marta Laganà, Massimo Terzolo, Salvatore Grisanti, Harm R. Haak, Hester Ettaieb, Rossella Libé, Internal Medicine, Promovendi PHPC, Health Services Research, RS: CAPHRI - R1 - Ageing and Long-Term Care, and Interne Geneeskunde
Subjects: Oncology, Male, Internationality, Hydrocortisone, Endocrinology, Diabetes and Metabolism, HYPERCORTISOLISM, Endocrinology, 80 and over, Adrenocortical Carcinoma, Adrenocortical carcinoma, Mitotane, Aged, 80 and over, TARGETED THERAPIES, Hazard ratio, Bone metastasis, General Medicine, Middle Aged, Diabetes and Metabolism, Denosumab, ZOLEDRONIC ACID, Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Bone Neoplasms, Female, Humans, Morbidity, Mortality, Retrospective Studies, Young Adult, CLINICAL-PRACTICE GUIDELINES, medicine.drug, medicine.medical_specialty, Lower risk, LUNG-CANCER, Internal medicine, medicine, MANAGEMENT, BREAST-CANCER, business.industry, Retrospective cohort study, medicine.disease, PHASE-III, Zoledronic acid, EUROPEAN NETWORK, PROSTATE-CANCER PATIENTS, business
Abstract: Introduction Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent. Objective The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis. Methods This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States. Results Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19–4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range. Conclusion Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.
Published: 2019

21. Prognosis of Malignant Pheochromocytoma and Paraganglioma (MAPP-Prono Study): A European Network for the Study of Adrenal Tumors Retrospective Study

Author: Christine Do Cao, S. Laboureau, Delphine Drui, Anne-Paule Gimenez-Roqueplo, Isabelle Borget, Martin Schlumberger, Laurence Amar, Patricia Niccoli, Christelle De La Fouchardiere, Henri J L M Timmers, Bruna Calsina, Antongiulio Faggiano, Massimo Mannelli, Eric Baudin, Rossella Libé, Martin Fassnacht, Ségolène Hescot, Felix Beuschlein, Philippe Caron, Delphine Vezzosi, Sophie Leboulleux, Françoise Borson-Chazot, Fernando Riccardi, Timo Deutschbein, Maria Currás-Freixes, Bernard Goichot, Letizia Canu, Antoine Tabarin, Jérôme Bertherat, Anouk van Berkel, Mercedes Robledo, and Nuria Valdés
Subjects: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Proliferative index, pheochromocytoma, paraganglioma, prognosis, overall survival, SDHB, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adrenal Gland Neoplasms, Malignancy, Biochemistry, Pheochromocytoma, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Endocrinology, Paraganglioma, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Univariate analysis, business.industry, Biochemistry (medical), Hazard ratio, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Metanephrines, Middle Aged, medicine.disease, Succinate Dehydrogenase, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Female, business
Abstract: BACKGROUND Malignant pheochromocytoma and paraganglioma (MPP) are characterized by prognostic heterogeneity. Our objective was to look for prognostic parameters of overall survival (OS) in MPP patients. PATIENTS AND METHODS Retrospective multicenter study of MPP characterized by a neck-thoraco-abdomino-pelvic CT or MRI at the time of malignancy diagnosis in European centers between 1998 and 2010. RESULTS One hundred sixty-nine patients from 18 European centers were included. Main characteristics of patients with MPP were: primary pheochromocytoma in 53% of patients; tumor- or hormone-related symptoms in 57% or 58% of cases; positive plasma or urine hormones in 81% of patients; identification of a mutation in SDHB in 42% of cases. Metastatic sites included bone (64%), lymph node (40%), lung (29%), and liver (26%); mean time between initial and malignancy diagnosis was 43 months (range, 0 to 614). Median follow-up was 68 months and median survival 6.7 years. Using univariate analysis, better survival was associated with head and neck paraganglioma, age
Published: 2019

22. Medical management of adrenocortical carcinoma: Current recommendations, new therapeutic options and future perspectives

Author: Frederic Castinetti, Vincent Amodru, Yves Reznik, Rossella Libé, Thierry Brue, Marie-Eve Garcia, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Marseille Maladies Rares (MarMaRa), and Gall, Valérie
Subjects: Oncology, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Immunothérapie, 030209 endocrinology & metabolism, Medical Oncology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Adrenocortical Carcinoma, medicine, Humans, Adrenocortical carcinoma, Chemotherapy, Mitotane, Adrenal, Etoposide, Cancer, Temozolomide, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Medical treatment, business.industry, Therapies, Investigational, Drugs, Investigational, General Medicine, Immunotherapy, medicine.disease, Adrenal Cortex Neoplasms, 3. Good health, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Surrénales, business, Chimiothérapie, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Adrenocortical carcinoma is a rare malignant tumor of poor prognosis, frequently requiring additional treatments after initial surgery. Due to its adrenolytic action, mitotane has become the first-line medical treatment in patients with aggressive adrenocortical carcinoma. Over the last 2 years, apart from the classical chemotherapy based on etoposide and platinum salts, several studies reported the use of drugs such as temozolomide, tyrosine kinase inhibitors or immunotherapy, with more or less convincing results. The aim of this review is to give further insights in the use of these drugs, and to describe potential therapeutic perspectives based on recent pangenomic studies, for the future management of these still difficult to treat tumors., Le corticosurrénalome malin est une tumeur rare, de mauvais pronostic, nécessitant fréquemment le recours à des traitements médicamenteux après la chirurgie initiale. Depuis de nombreuses années, le mitotane est le traitement de 1re ligne des corticosurrénalomes agressifs, du fait de ses propriétés adrénolytiques. Cependant, ce traitement est souvent insuffisant et associé à une chimiothérapie de type Etoposide/Platine. Au cours des 2 dernières années, plusieurs études ont rapporté l’efficacité plus ou moins probante de nouvelles molécules telles que le temozolomide, les inhibiteurs tyrosine kinase ou l’immunothérapie. L’objectif de cette revue est de préciser les résultats de ces différentes études, et d’apporter quelques données de perspectives basées sur les études pangénomiques, dans l’objectif de mieux appréhender ce que pourrait être la prise en charge de ces tumeurs dans les années à venir.
Published: 2021

23. LSD1/KDM1A Inactivation Causes Hereditary Food-Dependent Cushing’s Syndrome

Author: Maxime Barat, Bruno Ragazzon, Bertrand Dousset, Maria Candida Barisson Villares Fragoso, Patricia Vaduva, Constantine A. Stratakis, Rossella Libé, Marie-Odile North, Mathilde Sibony, Guillaume Assié, Anne Jouinot, Eric Letouzé, Florian Violon, Eric Pasmant, Philippe Emy, Igor Tauveron, Martin Reincke, Annabel Berthon, Magalie Haissaguerre, Karine Perlemoine, Fidéline Bonnet, Christopher Ribes, Isadora Cavalcante, Laurence Guignat, Lucas Bouys, Jérôme Bertherat, Lionel Groussin, Roberta Armignacco, Anna Vaczlavik, Gaetan Giannone, and Stéphanie Espiard
Subjects: History, animal structures, Polymers and Plastics, business.industry, Adrenalectomy, medicine.medical_treatment, Industrial and Manufacturing Engineering, Germline, Macronodular Adrenal Hyperplasia, DNA methylation, Cancer research, Medicine, Ectopic expression, Business and International Management, Allele, business, Exome sequencing, SNP array
Abstract: Purpose: To investigate the genetic cause of Food-dependent Cushing’s syndrome (FDCS) observed in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) and adrenal ectopic expression of the GIP receptor (GIPR). Germline ARMC5 alterations have been reported in about 25 % of PBMAH index cases but are absent in patients with FDCS. Methods: A multi-omics analysis of PBMAH tissues from 36 patients treated by adrenalectomy was performed (RNAseq, SNP array, methylome, miRNome, exome sequencing). Results: The integrative analysis revealed three molecular groups with different clinical features: G1, PBMAH due to ARMC5 inactivating variants; G2, with GIPR ectopic expression and FDCS; and G3, with a less severe phenotype. Exome sequencing revealed germline truncating variants of LSD1/KDM1A in the G2 group, constantly associated with a somatic loss of the LSD1/KDM1A wildtype allele on 1p, leading to a loss of LSD1/KDM1A expression both at mRNA and protein levels (p=1.2x10-12 and p
Published: 2021

24. An Ectopic Parathyroid Adenoma Mimicking a Carotid Body Paraganglioma

Author: Rossella Libé, Anne-Ségolène Cottereau, Sébastien Gaujoux, Julien Calvani, Tatiana Lecot Connan, Myriam Wartski, and Lionel Groussin
Subjects: medicine.medical_specialty, ectopic parathyroid adenoma, business.industry, Endocrinology, Diabetes and Metabolism, carotid body paraganglioma, 18F-FDOPA, Carotid Body Paraganglioma, 18F-Choline PET/CT, 18f fdopa, Image, medicine, Radiology, business, AcademicSubjects/MED00250, Ectopic parathyroid adenoma
Published: 2020

25. Genomic classification of benign adrenocortical lesions

Author: Bertrand Dousset, Simon Faillot, Anna Vaczlavik, Jean Guibourdenche, Lionel Groussin, Mathilde Sibony, Fideline Bonnet-Serrano, Stéphanie Espiard, Amandine Septier, Mario Neou, Ludivine Drougat, Marthe Rizk-Rabin, Bruno Ragazzon, Guillaume Assié, Simon Garinet, Thomas Foulonneau, Anne Jouinot, Windy Rondof, Rossella Libé, Karine Hecale-Perlemoine, Aurélien de Reyniès, Jérôme Bertherat, and Université de Paris, Institut Cochin, Institut National de la Santé et de la Recherche Médicale INSERM U1016, Centre National de la Recherche Scientifique CNRS UMR8104, F-75014 Paris.
Subjects: 0301 basic medicine, Cortisol secretion, Cancer Research, Adenoma, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, medicine, Humans, Epigenetics, Benign adrenal tumors, Exome, ComputingMilieux_MISCELLANEOUS, Genomics, Hyperplasia, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 030104 developmental biology, Oncology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, DNA methylation, Adrenocortical Adenoma, Cancer research
Abstract: Benign adrenal tumors cover a spectrum of lesions with distinct morphology and steroid secretion. Current classification is empirical. Beyond a few driver mutations, pathophysiology is not well understood. Here, a pangenomic characterization of benign adrenocortical tumors is proposed, aiming at unbiased classification and new pathophysiological insights. Benign adrenocortical tumors (n = 146) were analyzed by transcriptome, methylome, miRNome, chromosomal alterations and mutational status, using expression arrays, methylation arrays, miRNA sequencing, SNP arrays, and exome or targeted next-generation sequencing respectively. Pathological and hormonal data were collected for all tumors. Pangenomic analysis identifies four distinct molecular categories: (1) tumors responsible for overt Cushing, gathering distinct tumor types, sharing a common cAMP/PKA pathway activation by distinct mechanisms; (2) adenomas with mild autonomous cortisol excess and non-functioning adenomas, associated with beta-catenin mutations; (3) primary macronodular hyperplasia with ARMC5 mutations, showing an ovarian expression signature; (4) aldosterone-producing adrenocortical adenomas, apart from other benign tumors. Epigenetic alterations and steroidogenesis seem associated, including CpG island hypomethylation in tumors with no or mild cortisol secretion, miRNA patterns defining specific molecular groups, and direct regulation of steroidogenic enzyme expression by methylation. Chromosomal alterations and somatic mutations are subclonal, found in less than 2/3 of cells. New pathophysiological insights, including distinct molecular signatures supporting the difference between mild autonomous cortisol excess and overt Cushing, ARMC5 implication into the adreno-gonadal differentiation faith, and the subclonal nature of driver alterations in benign tumors, will orient future research. This first genomic classification provides a large amount of data as a starting point.
Published: 2020

26. Results of the ADIUVO Study, the First Randomized Trial on Adjuvant Mitotane in Adrenocortical Carcinoma Patients

Author: Hélène Lasolle, Maria Candida Barisson Villares Fragoso, Bénédicte Decoudier, Martin Fassnacht, Jérôme Bertherat, Tina Dušek, Rossella Libé, Letizia Canu, Irina Bancos, Alfredo Berruti, André Lacroix, Darko Kastelan, Marcus Quinkler, Paola Berchialla, Wiebke Arlt, Soraya Puglisi, Paola Loli, Harm R. Haak, Paola Perotti, Eric Baudin, Isabelle Bourdeau, Massimo Terzolo, Matthias Kroiss, and Felix Beuschlein
Subjects: Oncology, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, medicine.disease, law.invention, Therapeutic Trials and Prognostic Markers for Adrenal Diseases, Randomized controlled trial, law, Internal medicine, medicine, Adrenocortical carcinoma, Mitotane, Adrenal, business, Adjuvant, AcademicSubjects/MED00250, medicine.drug
Abstract: Background: The ESE-ENSAT guidelines on the management of adrenocortical carcinoma (ACC) suggest adjuvant mitotane for patients at high risk of recurrence following radical surgery. This indication has a limited evidence base, lacking results from randomized controlled trials. No suggestion for or against adjuvant mitotane in low-risk patients was given, since studies did not stratify patients for prognosis. The randomized controlled study ADIUVO compared the efficacy of adjuvant mitotane treatment vs. observation in prolonging recurrence-free survival (RFS) in ACC patients at low-intermediate risk of recurrence. Methods: The main inclusion criteria were: stage I-III ACC, R0 surgery, and Ki-67 ≤10%. Patients were randomly assigned 1:1 to adjuvant mitotane (MIT) or observation (OBS). The primary endpoint of the study was RFS. Patients who refused randomization were offered inclusion in the ADIUVO OBSERVATIONAL study. In this prospective, observational study, patients were managed as in the ADIUVO study. A total of 91 patients were enrolled in ADIUVO, 45 in the MIT and 46 in the OBS arm. Baseline characteristics of patients were perfectly matched between the 2 arms: median age, 51 vs. 50.5 years; female, 73% vs. 67%; stage I, 20% vs. 26%; stage II, 67% vs. 63%, stage III, 13% vs. 11%; ACC secretion 44% vs. 36%; Weiss 5 vs. 5; respectively. In ADIUVO OBSERVATIONAL, 42 patients were treated with mitotane and 53 were untreated. Baseline characteristics of patients were matched between the 2 groups and with MIT and OBS groups in ADIUVO. Thus, the ADIUVO OBSERVATIONAL cohorts could be analyzed in parallel to those of ADIUVO. Results: In the ADIUVO study, recurrences were 8 in the MIT and 11 in the OBS arm, while deaths were 2 and 5, respectively. RFS and overall survival (OS) did not significantly differ between the 2 arms. Tumor size was a predictor of RFS in multivariable analysis. In the OBS arm, the HR for recurrence was 1.321 (95%CI, 0.55–3.32, p=0.54) and HR for death 2.171 (95%CI, 0.52–12.12, p=0.29). The survival analysis in the ADIUVO OBSERVATIONAL study confirmed the findings of ADIUVO. Given the outcome of both studies, the NNT is 55. Conclusions: ACC patients at low-intermediate risk of recurrence after surgery are a minority; however, they show a far better prognosis than expected (5-year RFS is about 75%) and do not benefit significantly from adjuvant mitotane. The results of the ADIUVO study do not support routine use of adjuvant mitotane in this subset of patients, who may thus avoid a potentially toxic treatment. This is an important step toward personalization of ACC care.
Published: 2021

27. Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: A prospective test validation study

Author: Irina Bancos, Angela E Taylor, Vasileios Chortis, Alice J Sitch, Carl Jenkinson, Caroline J Davidge-Pitts, Katharina Lang, Stylianos Tsagarakis, Magdalena Macech, Anna Riester, Timo Deutschbein, Ivana D Pupovac, Tina Kienitz, Alessandro Prete, Thomas G Papathomas, Lorna C Gilligan, Cristian Bancos, Giuseppe Reimondo, Magalie Haissaguerre, Ljiljana Marina, Marianne A Grytaas, Ahmed Sajwani, Katharina Langton, Hannah E Ivison, Cedric H L Shackleton, Dana Erickson, Miriam Asia, Sotiria Palimeri, Agnieszka Kondracka, Ariadni Spyroglou, Cristina L Ronchi, Bojana Simunov, Danae A Delivanis, Robert P Sutcliffe, Ioanna Tsirou, Tomasz Bednarczuk, Martin Reincke, Stephanie Burger-Stritt, Richard A Feelders, Letizia Canu, Harm R Haak, Graeme Eisenhofer, M Conall Dennedy, Grethe A Ueland, Miomira Ivovic, Antoine Tabarin, Massimo Terzolo, Marcus Quinkler, Darko Kastelan, Martin Fassnacht, Felix Beuschlein, Urszula Ambroziak, Dimitra A Vassiliadi, Michael W O'Reilly, William F Young, Michael Biehl, Jonathan J Deeks, Wiebke Arlt, Stephan Glöckner, Richard O. Sinnott, Anthony Stell, Maria C. Fragoso, Ivana D. Pupovac, Sarah Cazenave, Jérôme Bertherat, Rossella Libé, Christina Brugger, Stefanie Hahner, Matthias Kroiss, Cristina L. Ronchi, Dimitra A. Vassiliadi, Vittoria Basile, Elisa Ingargiola, Massimo Mannelli, Hester Ettaieb, Harm R. Haak, Thomas M. Kerkhofs, Richard A. Feelders, Johannes Hofland, Leo J. Hofland, Marianne A. Grytaas, Eystein S. Husebye, Grethe A. Ueland, Malgorzata Zawierucha, Isabel Paiva, M. Conall Dennedy, Mark Sherlock, Rachel K. Crowley, Jonathan J. Deeks, Alice J. Sitch, Lorna C. Giligan, Beverly A. Hughes, Hannah E. Ivison, Konstantinos Manolopoulos, Donna M. O'Neil, Michael W. O'Reilly, Thomas G. Papathomas, Cedric H.L. Shackleton, Angela E. Taylor, Robert P. Sutcliffe, Peter Guest, Kassiani Skordilis, Alice Chang, Caroline J. Davidge-Pitts, Danae A. Delivanis, Neena Natt, Todd B. Nippoldt, Melinda Thomas, William F. Young Jr., Intelligent Systems, Interne Geneeskunde, RS: CAPHRI - R1 - Ageing and Long-Term Care, and Internal Medicine
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Adrenal Gland Neoplasms, SOCIETY, 030209 endocrinology & metabolism, Urine, adrenal incidentaloma, steroid metabolomics, adrenocortical carcinoma, Malignancy, Article, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Hounsfield scale, Diagnosis, Internal Medicine, Humans, Metabolomics, Medicine, Adrenocortical carcinoma, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, MALIGNANCY, Incidental Findings, medicine.diagnostic_test, business.industry, Europe, Female, Follow-Up Studies, Middle Aged, Steroids, Triple test, MASS-SPECTROMETRY, 16. Peace & justice, medicine.disease, 6. Clean water, 3. Good health, PREVALENCE, Differential, Histopathology, Differential diagnosis, business, Nuclear medicine
Abstract: Background: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. Methods: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs
Published: 2020

28. Modified GRAS score for prognostic classification of adrenocortical carcinoma: an ENSAT multicentre study

Author: Wiebke Arlt, Maria Candida Barisson Villares Fragoso, Jon Deeks, Yasir S Elhassan, Darko Kastelan, Harm R. Haak, Harriet Cook, Magalie Haissaguerre, Rossella Libé, Paola Loli, Sarah Berhane, Jérôme Bertherat, Barbara Altieri, Otilia Kimpel, Deborah Cosentini, Marta Laganà, Anna Calabrese, Alfredo Berruti, Massimo Terzolo, Eric Baudin, Letizia Canu, Martin Fassnacht, and Cristina L Ronchi
Subjects: Oncology, medicine.medical_specialty, Prognostic classification, business.industry, Internal medicine, medicine, Adrenocortical carcinoma, medicine.disease, business
Published: 2020

29. Identification of transcriptome profiles in paraffin samples using 3’ RNA-sequencing for the prognostic assessment of adrenocortical carcinoma

Author: Jérôme Bertherat, Roberta Armignacco, Lionel Groussin, Sébastien Gaujoux, Brigitte Izac, Franck Letourneur, Amandine Septier, Guillaume Assié, Mathilde Sibony, Karen Leroy, Karine Perlemoine, Bertrand Dousset, Anne Jouinot, Rossella Libé, Lindsay Jeanpierre, Bruno Ragazzon, and Murat Daniel De
Subjects: medicine, Adrenocortical carcinoma, RNA, Transcriptome Profiles, Identification (biology), Computational biology, Biology, medicine.disease
Published: 2020

30. Intratumor heterogeneity of prognostic DNA-based molecular markers in adrenocortical carcinoma

Author: Mario Neou, Bertrand Dousset, Cristina L Ronchi, Sébastien Gaujoux, Juliane Lippert, Anne Jouinot, Bruno de La Villéon, Rossella Libé, Jérôme Bertherat, Lionel Groussin, Karine Perlemoine, Amandine Septier, Silke Appenzeller, Mathilde Sibony, Guillaume Assié, and Martin Fassnacht
Subjects: 0301 basic medicine, Endocrinology, Diabetes and Metabolism, intratumor heterogeneity, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Germline mutation, CDKN2A, Internal Medicine, adrenocortical carcinoma, chromosome alterations, Medicine, Adrenocortical carcinoma, lcsh:RC648-665, business.industry, Research, Chromosome, Methylation, medicine.disease, Primary tumor, 030104 developmental biology, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, somatic mutations, methylation, business
Abstract: Background: The prognosis of adrenocortical carcinoma (ACC) is heterogeneous. Genomic studies have identified ACC subgroups characterized by specific molecular alterations, including features measured at DNA level (somatic mutations, chromosome alterations, DNA methylation), which are closely associated with outcome. The aim of this study was to evaluate intratumor heterogeneity of prognostic molecular markers at the DNA level. Methods: Two different tissue samples (primary tumor, local recurrence or metastasis) were analyzed in 26 patients who underwent surgery for primary or recurrent ACC. DNA-related biomarkers with prognostic role were investigated in frozen and paraffin-embedded samples. Somatic mutations of p53/Rb and Wnt/β-catenin pathways were assessed using next-generation sequencing (n = 26), chromosome alteration profiles were determined using SNP arrays (n = 14) and methylation profiles were determined using four-gene bisulfite pyrosequencing (n = 12). Results: Somatic mutations for ZNRF3, TP53, CTNN1B and CDKN2A were found in 7, 6, 6 and 4 patients, respectively, with intratumor heterogeneity in 8/26 patients (31%). Chromosome alteration profiles were ‘Noisy’ (numerous and anarchic alterations) in 8/14 and ‘Chromosomal’ (extended patterns of loss of heterozygosity) in 5/14 of the study samples. For these profiles, no intratumor heterogeneity was observed. Methylation profiles were hypermethylated in 5/12 and non-hypermethylated in 7/12 of the study samples. Intratumor heterogeneity of methylation profiles was observed in 2/12 patients (17%). Conclusions: Intratumor heterogeneity impacts DNA-related molecular markers. While somatic mutation can differ, prognostic DNA methylation and chromosome alteration profile seem rather stable and might be more robust for the prognostic assessment.
Published: 2020

31. Combined 68Ga-DOTATOC and 18F-FDG PET Predicts a Double Component With Different Grade of a Pancreatic Neuroendocrine Tumor in a Patient With Multiple Endocrine Neoplasia Type 1

Author: Céline Meyer, Anne-Cécile Paepegaey, Rossella Libé, Sébastien Gaujoux, and Alexandre Rouquette
Subjects: Adult, Male, medicine.medical_specialty, Pancreatic neuroendocrine tumor, Neuroendocrine tumors, Octreotide, 030218 nuclear medicine & medical imaging, 18f fdg pet, 68ga dotatoc, 03 medical and health sciences, 0302 clinical medicine, Fluorodeoxyglucose F18, medicine, Multiple Endocrine Neoplasia Type 1, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Multiple endocrine neoplasia, Lower grade, business.industry, General Medicine, medicine.disease, Prognosis, Pancreatic Neoplasms, Neuroendocrine Tumors, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Radiology, business
Abstract: Managing decisions of pancreatic neuroendocrine tumors (pNETs) can be challenging because of different clinical presentations and prognosis. A 31-year-old woman with multiple endocrine neoplasia type 1, including a suspicious pNET, was assessed with Ga-DOTATOC and F-FDG PET. A high Ga-DOTATOC uptake was visualized in the entire pNET, whereas a high F-FDG PET uptake was present only in the upper part of the tumor. After surgery, pathology confirmed the pNET with a double component: an upper grade 2 with a Ki67 of 11% with the high F-FDG PET uptake, and a lower grade 1 with a Ki67 of 2%. Combined Ga-DOTATOC/F-FDG PET predicts the grade in heterogeneous pNETs.
Published: 2020

32. Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma

Author: Joël Coste, Antoine Tabarin, Karine Perlemoine, Louis Jacob, Ronald R. de Krijger, Simon Garinet, Jens Waldmann, Olivier Chabre, Mathilde Sibony, Felix Beuschlein, Magalie Haissaguerre, Bertrand Dousset, Nadim Hamzaoui, Bruno de La Villéon, Bruno Ragazzon, Anne Jouinot, Laurence Amar, Martin Fassnacht, Esther Korpershoek, Massimo Mannelli, Xavier Bertagna, Rossella Libé, Marcus Quinkler, Frédérique Tissier, Guillaume Assié, Jérôme Bertherat, Matthias Kroiss, Julien Sakat, Lionel Groussin, Eric Baudin, Michaela Luconi, Cristina L Ronchi, Silviu Sbiera, Mario Neou, Sébastien Gaujoux, and Pathology
Subjects: Oncology, medicine.medical_specialty, Cancer Research, Mitotic index, Proliferation index, business.industry, Hazard ratio, medicine.disease, BUB1B, 03 medical and health sciences, GSTP1, 0302 clinical medicine, Interquartile range, 030220 oncology & carcinogenesis, Internal medicine, medicine, Adjuvant therapy, Adrenocortical carcinoma, 030212 general & internal medicine, business, Original Investigation
Abstract: IMPORTANCE: The risk stratification of adrenocortical carcinoma (ACC) based on tumor proliferation index and stage is limited. Adjuvant therapy after surgery is recommended for most patients. Pan-genomic studies have identified distinct molecular groups closely associated with outcome. OBJECTIVE: To compare the molecular classification for prognostic assessment of ACC with other known prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective biomarker analysis, ACC tumor samples from 368 patients who had undergone surgical tumor removal were collected from March 1, 2005, to September 30, 2015 (144 in the training cohort and 224 in the validation cohort) at 21 referral centers with a median follow-up of 35 months (interquartile range, 18-74 months). Data were analyzed from March 2016 to March 2018. EXPOSURES: Meta-analysis of pan-genomic studies (transcriptome, methylome, chromosome alteration, and mutational profiles) was performed on the training cohort. Targeted biomarker analysis, including targeted gene expression (BUB1B and PINK1), targeted methylation (PAX5, GSTP1, PYCARD, and PAX6), and targeted next-generation sequencing, was performed on the training and validation cohorts. MAIN OUTCOMES AND MEASURES: Disease-free survival. Cox proportional hazards regression and C indexes were used to assess the prognostic value of each model. RESULTS: Of the 368 patients (mean [SD] age, 49 [16] years), 144 were in the training cohort (100 [69.4%] female) and 224 were in the validation cohort (142 [63.4%] female). In the training cohort, pan-genomic measures classified ACC into 3 molecular groups (A1, A2, and A3-B), with 5-year survival of 9% for group A1, 45% for group A2, and 82% for group A3-B (log-rank P
Published: 2019

33. MiR-483-5p and miR-139-5p promote aggressiveness by targeting N-myc downstream-regulated gene family members in adrenocortical cancer

Author: Claire Agosta, Olivier Chabre, Jérôme Bertherat, Laurent Guyon, Bruno Boisson, Nadia Cherradi, Jean-Jacques Feige, Rossella Libé, Josiane Denis, Nathalie Sturm, and Jonathan Laugier
Subjects: 0301 basic medicine, Cancer Research, Effector, Cell, Biology, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Oncology, Downregulation and upregulation, 030220 oncology & carcinogenesis, microRNA, Cancer research, medicine, Adrenocortical carcinoma, Gene family, Ectopic expression, N-Myc
Abstract: Adrenocortical carcinoma (ACC) is a tumor with poor prognosis in which overexpression of a panel of microRNAs has been associated with malignancy but a very limited number of investigations on their role in ACC pathogenesis have been conducted. We examined the involvement of miR-483-5p and miR-139-5p in adrenocortical cancer aggressiveness. Using bioinformatics predictions and mRNA/miRNA expression profiles, we performed an integrated analysis to identify inversely correlated miRNA-mRNA pairs in ACC. We identified N-myc downstream-regulated gene family members 2 and 4 (NDRG2 and NDRG4) as targets of miR-483-5p and miR-139-5p, respectively. NDRG2 and NDRG4 expressions were inversely correlated respectively with miR-483-5p and miR-139-5p levels in aggressive ACC samples from two independent cohorts of 20 and 44 ACC. Moreover, upregulation of miR-139-5p and downregulation of NDRG4 demonstrated a striking prognostic value. A direct interaction between miR-483-5p or miR-139-5p and their targets was demonstrated in reporter assays. Downregulation of miR-483-5p or miR-139-5p in the ACC cell lines NCI-H295R and SW13 increased NDRG2 or NDRG4 mRNA and protein expression, compromised adrenocortical cancer cell invasiveness and anchorage-independent growth. MiR-483-5p or miR-139-5p overexpression and NDRG2 or NDRG4 inhibition produce similar changes, which are rescued by NDRG2 or NDRG4 ectopic expression. We established that key factors mediating epithelial-to-mesenchymal transition are downstream effectors of miR-483-5p/NDRG2 and miR-139-5p/NDRG4 pathways. Collectively, our data show for the first time that miR-483-5p/NDRG2 and miR-139-5p/NDRG4 axes promote ACC aggressiveness, with potential implications for prognosis and therapeutic interventions in adrenocortical malignancies.
Published: 2018

34. Correction to: A pheochromocytoma wrapped in an IgG4-related disease

Author: Anne-Ségolène Cottereau, Marie-Francoise Triller, Anne-Cécile Paepegaey, Sébastien Gaujoux, Mathilde Sibony, Lionel Groussin, Rossella Libé, and Anthony Dohan
Subjects: Pheochromocytoma, medicine.medical_specialty, business.industry, medicine, Radiology, Nuclear Medicine and imaging, IgG4-related disease, General Medicine, Radiology, medicine.disease, business
Published: 2020

35. Reversal of a Blunted Follicle-Stimulating Hormone by Chemotherapy in an Inhibin B–Secreting Adrenocortical Carcinoma

Author: Najiba Lahlou, Stéphanie Espiard, Estelle Louiset, Bertrand Dousset, Marie Bienvenu, Mathilde Sibony, Lionel Groussin, Jérôme Bertherat, Rossella Libé, Institut Cochin (IC 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), Laboratoire de Biologie hormonale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul, 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), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), [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), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gynécologie et d'endocrinologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Saint-Vincent de Paul, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)
Subjects: medicine.medical_specialty, endocrine system, Endocrinology, Diabetes and Metabolism, education, 030209 endocrinology & metabolism, Gonadotropin-releasing hormone, Case Reports, inhibin B, 03 medical and health sciences, Follicle-stimulating hormone, Cushing syndrome, 0302 clinical medicine, Internal medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, adrenocortical carcinoma, Adrenocortical carcinoma, Mitotane, Adrenal, business.industry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Endocrinology, 030220 oncology & carcinogenesis, tumor marker, business, Luteinizing hormone, Immunostaining, hormones, hormone substitutes, and hormone antagonists, Hormone, medicine.drug
Abstract: Context: Adrenocortical carcinomas (ACCs) are revealed in 60% of cases by steroid hypersecretion. Alternatively, it is uncommon to observe a paraneoplastic syndrome due to a peptide oversecretion. Case Description: We describe a 60-year-old man with a right adrenal mass. Hormonal evaluation showed an ACTH-independent Cushing syndrome. Surprisingly, follicle-stimulating hormone (FSH) levels were suppressed and blunted during gonadotropin-releasing hormone stimulation, despite normal luteinizing hormone levels. Levels of inhibin B, which negatively regulates the pituitary FSH, were very high. Given the atypical hormonal findings, an adrenal mass biopsy was performed, which allowed the diagnosis of an adrenocortical tumor (positive for steroidogenic factor-1 immunostaining). Moreover, an intense α-inhibin subunit immunostaining was observed. Because of the presence of metastases, the patient received mitotane and chemotherapy (etoposide and cisplatin). After 2 cycles, the inhibin B dropped. After 5 cycles, tumor size was reduced by 15%. Inhibin B levels remained low, and basal and gonadotropin-releasing hormone–stimulated FSH levels normalized. The patient underwent tumor resection, and pathology confirmed the ACC diagnosis (Weiss score of 9). The intensity of the α-inhibin subunit immunostaining was significantly decreased. Conclusions: We report the case of an inhibin B–secreting ACC in which the response to chemotherapy and mitotane was associated with a normalization of inhibin B secretion, allowing the reversal of the blunted FSH secretion. Inhibin B should be measured in case of suppressed FSH levels despite normal luteinizing hormone levels and may be considered a tumoral marker in some ACCs, even during treatment follow-up., Precis: We studied an adrenal mass with suppressed FSH levels, blunted after GnRH stimulation, and found an inhibin B–secreting adrenocortical carcinoma, in which inhibin B was normalized after chemotherapy.
Published: 2017

36. Letter to the Editor from Berthon: 'Cardiac Myxoma Caused by Fumarate Hydratase Gene Deletion in Patient With Cortisol-Secreting Adrenocortical Adenoma'

Author: Annabel Berthon, Jérôme Bertherat, Constantine A. Stratakis, and Rossella Libé
Subjects: medicine.medical_specialty, Letter to the editor, business.industry, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Myxoma, Gene deletion, medicine.disease, Biochemistry, Adrenocortical adenoma, Endocrinology, Internal medicine, Medicine, Fumarate Hydratase Gene, In patient, business, Hydrocortisone, medicine.drug
Published: 2020

37. A pheochromocytoma wrapped in an IgG4-related disease

Author: Marie-Francoise Triller, Rossella Libé, Mathilde Sibony, Lionel Groussin, Anne-Ségolène Cottereau, Anthony Dohan, Anne-Cécile Paepegaey, and Sébastien Gaujoux
Subjects: medicine.medical_specialty, business.industry, Adrenal Gland Neoplasms, MEDLINE, Pheochromocytoma, General Medicine, medicine.disease, Immunoglobulin G, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, IgG4-related disease, Immunoglobulin G4-Related Disease, business
Published: 2020

38. Contribution of morphological and functional liver imaging to differentiate liver metastases of adrenocortical carcinoma from those of neuroendocrine tumors in a woman with a final diagnosis of multiple endocrine neoplasia type 1

Author: Ingrid Cirederf, Anne-Cécile Paepegaey, Eddy Glaude, Rossella Libé, Fritz-Line Velayoudom, Abdoulaye Diedhiou, and Lyonel Belia
Subjects: Pathology, medicine.medical_specialty, business.industry, Medicine, Adrenocortical carcinoma, Neuroendocrine tumors, business, Multiple endocrine neoplasia, medicine.disease, Liver imaging
Published: 2019

39. Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma

Author: Lucile Offredo, Delphine Zenaty, Eric Baudin, Antoine Tabarin, Peggy Pierre, Alexandre Buffet, Anne-Paule Gimenez-Roqueplo, Philippe Herman, Igor Tauveron, Frédéric Chabolle, Judith Favier, Olivier Chabre, Laurence Amar, Christiane Ajzenberg, Rossella Libé, Yves Reznik, Brigitte Delemer, Bernard Goichot, Delphine Vezzosi, Laurene Ben Aim, Julien Hadoux, Delphine Drui, Vincent Darrouzet, Sandrine Laboureau, Sophie Leboulleux, Isabelle Raingeard, Jean-Louis Sadoul, Daniele Bernardeschi, Annabelle Esvant, Bertrand Cariou, Hervé Lefebvre, Jérôme Bertherat, Rachel Desailloud, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Toulouse [Toulouse], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Foch [Suresnes], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Amiens-Picardie, Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Lapeyronie [Montpellier] (CHU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Archet 2 [Nice] (CHU), Université Paris-Saclay, CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, AP-HP Hôpital universitaire Robert-Debré [Paris], Université de Paris - UFR Pharmacie [Santé] (UP UFR Pharmacie), Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Endocrinologie [Nantes], Service d'Endocrinologie (TOULOUSE - Endocrino), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Information sur la Surdité et l'Implant Cochléaire [Paris] (CISIC), CHU Pitié-Salpêtrière [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), 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), Service d'oto-rhino-laryngologie, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'endocrinologie, CHU Grenoble-Hôpital Michallon, Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Endocrinologie (AMIENS - Endocrino), Service de Médecine Interne, Endocrinologie et Nutrition [CHU Strasbourg], CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS), Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, Institut Scientifique de Santé Publique [Belgique] - Scientific Institute of Public Health [Belgium] (WIV-ISP), Réseau International des Instituts Pasteur (RIIP), Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU), Service d'Endocrinologie (TOURS - Endocrino), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Endocrinologie - Diabétologie [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), Service d'Endocrinologie (NICE - Endocrino), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'Endocrinologie (BORDEAUX - Endocrino), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Gustave Roussy (IGR), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (UMR_S567 / UMR 8104), 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 Cochin (IC 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), Réhabilitation Chirurgicale mini-Invasive et Robotisée de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne - Diabète et Maladies métaboliques [Hôpital Hautepierre-Strasbourg]], Hôpital de Hautepierre [Strasbourg], Laboratoire de Neurobiologie des Réseaux Sensorimoteurs (LNRS), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5), Service d'Endocrinologie (MONTPELLIER - Endocrino), Collège de France (CDF), Collège de France (CdF), Développement et évolution (DE), Université Paris-Sud - Paris 11 (UP11)-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 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Les Hôpitaux Universitaires de Strasbourg (HUS)-CHU Strasbourg, Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), 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)-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)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), 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), Unité de recherche de l'institut du thorax (ITX-lab), Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Oncology, Male, SDHB, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adrenal Gland Neoplasms, Aftercare, Kaplan-Meier Estimate, Biochemistry, Neoplasms, Multiple Primary, 0302 clinical medicine, Endocrinology, Paraganglioma, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Child, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, Succinate Dehydrogenase, Survival Rate, Von Hippel-Lindau Tumor Suppressor Protein, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, Adolescent, 030209 endocrinology & metabolism, Context (language use), Pheochromocytoma, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Young Adult, Germline mutation, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Genetic Testing, Germ-Line Mutation, Genetic testing, Aged, Retrospective Studies, business.industry, Biochemistry (medical), Retrospective cohort study, Genetic Status, medicine.disease, Lost to Follow-Up, SDHD, business, Follow-Up Studies
Abstract: International audience; OC5.1Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytomaContextParagangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumors, characterized by a strong genetic component. Indeed, up to 40% of patients carry a germline mutation in a PPGL susceptibility gene. In accordance with the international recommendations, genotyping of PPGL susceptibility genes is therefore proposed to all patients with PPGL, but it has actually never beenshown whether the identification of a germline mutation in one PPGL susceptibility gene changes the outcome of mutation-carriers.ObjectiveOur objective was to evaluate how a positive genetic test impacts the management and outcome of propositus patients with PPGL carrying a germline mutation in one of the four major PPGL susceptibility genes (SDHB, SDHD, SDHC and VHL).DesignWe performed a multicentric retrospective study on 221 propositus carrying a SDHB, SDHD, SDHC or VHL germline mutation and followed in 24 French clinical centers of the Group of Endocrine Tumors and/or the COMETE network. Patients were divided into two groups: Genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and Historic patients who only benefited from the genetic test several years after initial PPGL diagnosis.ResultsCompared to Historic patients, Genetic patients had a better follow-up, with a higher number of examinations and a reduced number of patients lost to follow-up (9.6% versus 72%). During follow-up, smaller (18.7 mm versus 27.6, PZ0.0128) new PPGL and metastases as well as lower metastatic spread were observed in Genetic patients. Importantly, these differences were reversed in the Historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival than Historic ones (PZ0.0127).ConclusionAltogether our study clearly shows the positive impact of the identification of an SDHx or VHL mutation in the management, clinical outcome and survival of patients with PPGL. It reveals, for the first time, the clinical benefits of the practice of oncogenetics for patients with a rare cancer and strongly strengthens the recommendations of the Endocrine Society to consider PPGL genetic testingin all patients affected by PPGL.DOI: 10.1530/endoabs.63.OC5.1
Published: 2019

40. 18F-FDG PET reveals an adrenocortical carcinoma in a bilateral adrenal multinodular disease

Author: Jean-François Jazeron, Rossella Libé, Estelle Louiset, Lionel Groussin, 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), Centre Hospitalier de La Rochelle (CHR), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)
Subjects: Adrenal Cortex Diseases, Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Disease, MESH: Adrenal Cortex Neoplasms, 030218 nuclear medicine & medical imaging, 18f fdg pet, 03 medical and health sciences, MESH: Adrenocortical Carcinoma, 0302 clinical medicine, Endocrinology, X ray computed, Fluorodeoxyglucose F18, MESH: Fluorodeoxyglucose F18, Diabetes mellitus, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Adrenocortical Carcinoma, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Adrenocortical carcinoma, Humans, ComputingMilieux_MISCELLANEOUS, MESH: Adrenalectomy, MESH: Humans, MESH: Middle Aged, medicine.diagnostic_test, business.industry, Adrenalectomy, MESH: Adrenal Cortex Diseases, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Adrenal Cortex Neoplasms, MESH: Male, MESH: Positron-Emission Tomography, 3. Good health, Positron emission tomography, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Tomography, Radiopharmaceuticals, Nuclear medicine, business, Tomography, X-Ray Computed, MESH: Tomography, X-Ray Computed, MESH: Radiopharmaceuticals
Abstract: International audience
Published: 2019

41. Preoperative Detection of Liver Involvement by Right-Sided Adrenocortical Carcinoma Using CT and MRI

Author: Guillaume Assié, Jérôme Bertherat, Sébastien Gaujoux, Lionel Groussin Rouiller, Anne Jouinot, Rossella Libé, Maxime Barat, Mathilde Sibony, Philippe Soyer, Anthony Dohan, and Alice Kedra
Subjects: Cancer Research, medicine.medical_treatment, 030209 endocrinology & metabolism, liver, lcsh:RC254-282, Article, 03 medical and health sciences, hepatectomy, 0302 clinical medicine, adrenocortical carcinoma, neoplasm, staging, Medicine, Adrenocortical carcinoma, In patient, Receiver operating characteristic, business.industry, En bloc resection, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Oncology, 030220 oncology & carcinogenesis, Hepatectomy, business, Nuclear medicine, Kappa, Preoperative imaging
Abstract: Simple Summary The major prognosis factor of adrenocortical carcinoma is the completeness of surgery. Focal adrenocortical carcinoma bulge on computed tomography and adrenocortical carcinoma contour disruption on magnetic resonance imaging are highly reproducible signs. These signs are strongly associated with direct liver involvement by right-sided adrenocortical carcinoma on preoperative imaging. These findings may help surgeons plan surgical approach before resection and decrease the complication rate. Abstract The major prognosis factor of adrenocortical carcinoma (ACC) is the completeness of surgery. The aim of our study was to identify preoperative imaging features associated with direct liver involvement (DLI) by right-sided ACC. Two radiologists, blinded to the outcome, independently reviewed preoperative CT and MRI examinations for eight signs of DLI, in patients operated for right-sided ACC and retrospectively included from November 2007 to January 2020. DLI was confirmed using surgical and histopathological findings. Kappa values were calculated. Univariable and multivariable analyses were performed by using a logistic regression model. Receiver operating characteristic (ROC) curves were built for CT and MRI. Twenty-nine patients were included. Seven patients had DLI requiring en bloc resection. At multivariable analysis, focal ACC bulge was the single independent sign associated with DLI on CT (OR: 60.00; 95% CI: 4.60–782.40; p < 0.001), and ACC contour disruption was the single independent sign associated with DLI on MRI (OR: 126.00; 95% CI: 6.82–2328.21; p < 0.001). Both signs were highly reproducible, with respective kappa values of 0.85 and 0.91. The areas under ROC curves of MRI and CT models were not different (p = 0.838). Focal ACC bulge on CT and ACC contour disruption on MRI are independent and highly reproducible signs, strongly associated with DLI by right-sided ACC on preoperative imaging. MRI does not improve the preoperative assessment of DLI by comparison with CT.
Published: 2021

42. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Author: Siyuan Zheng, Andrew D. Cherniack, Ninad Dewal, Richard A. Moffitt, Ludmila Danilova, Bradley A. Murray, Antonio M. Lerario, Tobias Else, Theo A. Knijnenburg, Giovanni Ciriello, Seungchan Kim, Guillaume Assie, Olena Morozova, Rehan Akbani, Juliann Shih, Katherine A. Hoadley, Toni K. Choueiri, Jens Waldmann, Ozgur Mete, A. Gordon Robertson, Hsin-Ta Wu, Benjamin J. Raphael, Lina Shao, Matthew Meyerson, Michael J. Demeure, Felix Beuschlein, Anthony J. Gill, Stan B. Sidhu, Madson Q. Almeida, Maria C.B.V. Fragoso, Leslie M. Cope, Electron Kebebew, Mouhammed A. Habra, Timothy G. Whitsett, Kimberly J. Bussey, William E. Rainey, Sylvia L. Asa, Jérôme Bertherat, Martin Fassnacht, David A. Wheeler, Gary D. Hammer, Thomas J. Giordano, Roel G.W. Verhaak, Guillaume Assié, Hsin-Tu Wu, Madson Almeida, Maria Candida Barisson Fragoso, Mouhammed Amir Habra, Christopher Benz, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Yaron S.N. Butterfield, Rebecca Carlsen, Noreen Dhalla, Ranabir Guin, Robert A. Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Haiyan I. Li, Lynette Lim, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Peter J. Park, Matthias Kroiss, Jianjiong Gao, Chris Sander, Nikolaus Schultz, Corbin D. Jones, Raju Kucherlapati, Piotr A. Mieczkowski, Joel S. Parker, Charles M. Perou, Donghui Tan, Umadevi Veluvolu, Matthew D. Wilkerson, D. Neil Hayes, Marc Ladanyi, Marcus Quinkler, J. Todd Auman, Ana Claudia Latronico, Berenice B. Mendonca, Mathilde Sibony, Zack Sanborn, Michelle Bellair, Christian Buhay, Kyle Covington, Mahmoud Dahdouli, Huyen Dinh, Harsha Doddapaneni, Brittany Downs, Jennifer Drummond, Richard Gibbs, Walker Hale, Yi Han, Alicia Hawes, Jianhong Hu, Nipun Kakkar, Divya Kalra, Ziad Khan, Christine Kovar, Sandy Lee, Lora Lewis, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Liu Xi, Bertrand Dousset, Lionel Groussin, Rossella Libé, Lynda Chin, Sheila Reynolds, Ilya Shmulevich, Sudha Chudamani, Jia Liu, Laxmi Lolla, Ye Wu, Jen Jen Yeh, Saianand Balu, Tom Bodenheimer, Alan P. Hoyle, Stuart R. Jefferys, Shaowu Meng, Lisle E. Mose, Yan Shi, Janae V. Simons, Matthew G. Soloway, Junyuan Wu, Wei Zhang, Kenna R. Mills Shaw, John A. Demchok, Ina Felau, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Tanja Davidsen, Catherine Crawford, Carolyn M. Hutter, Heidi J. Sofia, Jeffrey Roach, Wiam Bshara, Carmelo Gaudioso, Carl Morrison, Patsy Soon, Shelley Alonso, Julien Baboud, Todd Pihl, Rohini Raman, Qiang Sun, Yunhu Wan, Rashi Naresh, Harindra Arachchi, Rameen Beroukhim, Scott L. Carter, Juok Cho, Scott Frazer, Stacey B. Gabriel, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Michael S. Noble, Gordon Saksena, Steven E. Schumacher, Carrie Sougnez, Doug Voet, Hailei Zhang, Jay Bowen, Sara Coppens, Julie M. Gastier-Foster, Mark Gerken, Carmen Helsel, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Stephen Baylin, James G. Herman, Janine LoBello, Aprill Watanabe, David Haussler, Amie Radenbaugh, Arjun Rao, Jingchun Zhu, Detlef K. Bartsch, Silviu Sbiera, Bruno Allolio, Timo Deutschbein, Cristina Ronchi, Victoria M. Raymond, Michelle Vinco, Linda Amble, Moiz S. Bootwalla, Phillip H. Lai, David J. Van Den Berg, Daniel J. Weisenberger, Bruce Robinson, Zhenlin Ju, Hoon Kim, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kanishka Sircar, Qianghu Wang, Kosuke Yoshihara, Peter W. Laird, Yu Fan, Wenyi Wang, Eve Shinbrot, Martin Reincke, John N. Weinstein, Sam Meier, and Timothy Defreitas
Subjects: Adult, Male, 0301 basic medicine, Cancer Research, Adolescent, Genomics, Biology, Genome, TERF2, Article, Disease-Free Survival, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Outcome Assessment, Health Care, Adrenocortical Carcinoma, medicine, Humans, Adrenocortical carcinoma, Genetic Predisposition to Disease, Child, Aged, Aged, 80 and over, Genetics, Genome, Human, business.industry, Gene Expression Profiling, Cell Biology, DNA Methylation, Middle Aged, Prognosis, medicine.disease, Adrenal Cortex Neoplasms, Human genetics, 3. Good health, Gene Expression Regulation, Neoplastic, Gene expression profiling, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer cell, DNA methylation, Cancer research, Female, Human genome, business
Abstract: We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.
Published: 2016

43. Clinical and molecular prognostic factors in adrenocortical carcinoma

Author: Rossella Libé
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, MEDLINE, Gene mutation, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Internal Medicine, medicine, Adrenocortical Carcinoma, Adrenocortical carcinoma, Humans, Stage (cooking), Pathological, business.industry, Incidence (epidemiology), medicine.disease, Prognosis, Adrenal Cortex Neoplasms, 030104 developmental biology, Molecular Diagnostic Techniques, 030220 oncology & carcinogenesis, Immunohistochemistry, Personalized medicine, business
Abstract: Introduction Adrenocortical carcinoma (ACC) is a rare cancer, with an incidence less than 0.7-1.5 per 1 million people per year, with a poor prognosis. The overall survival (OS) depends on the ENSAT stage: in particular in metastatic ACC the OS varies from 10 to 20 months, with a 5-year survival around 10%. ACC has a different behavior, probably due to a different biology. For this reason, a careful prognostic classification is mandatory, in order to stratify the patients and propose a specific management. Evidence acquisition Prognostic factors can be divides in three groups: clinical factors (tumor stage, age, hormone-related symptoms), pathological factors (Weiss Score, mitotic count, Ki-67, SF-1 and AVA2, P53, beta-catenin immunohistochemistry, resection status), molecular factors (chromosomal aberrations, methylation profile, altered gene expression and miRNA expression, gene mutations). Evidence synthesis The best way to stratify ACC patients and propose the best therapeutic option is to combine clinical, pathological and molecular factors. Conclusions Individualizing patients' prognosis and tumor biology appears as a necessary step for personalized medicine. In addition to tumor stage and tumor grade, the genomic classification may precise the risk stratification and thus help defining therapeutic strategy.
Published: 2018

44. Molecular classification of benign adrenocortical tumors: an integrated genomic study

Author: Marthe Rizk-Rabin, Anna Vaczlavik, Lionel Groussin, Stéphanie Espiard, Frédérique Tissier, Windy Luscap-Rondof, Jérôme Bertherat, S. Faillot, Mario Neou, Guillaume Assié, Simon Garinet, Ludivine Drougat, Rossella Libé, Fernande René-Corail, Anne Jouinot, Karine Perlemoine, Reynies Aurelien de, and Bruno Ragazzon
Subjects: Molecular classification, Computational biology, Biology
Published: 2018

45. Detection and monitoring of circulating tumor DNA in adrenocortical carcinoma

Author: Mario Neou, Olivier Soubrane, Guillaume Assié, Lucie Orhant, Juliana Pipoli da Fonseca, Franck Letourneur, Jérôme Bertherat, Anne Jouinot, Eric Pasmant, Lionel Groussin, Rossella Libé, Bertrand Dousset, Juliette Nectoux, Karine Perlemoine, Léopoldine Bricaire, Simon Garinet, Mathilde Sibony, Service de parasitologie - mycologie [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), 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), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biochimie et biologie moléculaire, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie hepato-pancreato-biliaire, 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), Institut Cochin (UMR_S567 / UMR 8104), 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)
Subjects: 0301 basic medicine, Adult, Male, Cancer Research, Sequence analysis, Endocrinology, Diabetes and Metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Circulating Tumor DNA, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, X ray computed, Adrenocortical Carcinoma, Medicine, Adrenocortical carcinoma, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, business.industry, Sequence Analysis, DNA, Middle Aged, medicine.disease, Adrenal Cortex Neoplasms, 030104 developmental biology, Oncology, chemistry, Circulating tumor DNA, Cancer research, Female, business, Tomography, X-Ray Computed, DNA
Abstract: International audience
Published: 2018

46. 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

47. Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term Survivors

Author: Martin Schlumberger, Amandine Berdelou, Antoine Tabarin, Claire Briet, Jérôme Bertherat, Christine Do Cao, Françoise Borson-Chazot, Philippe Caron, Delphine Drui, Christelle De La Fouchardiere, Bodale Djobo, Ségolène Hescot, Vanina Bongard, Magali Haissaguerre, Eric Baudin, Frédéric Illouz, Rossella Libé, Delphine Vezzosi, and Sophie Leboulleux
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Systemic therapy, Disease-Free Survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Randomized controlled trial, law, Internal medicine, Partial response, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Adrenocortical Carcinoma, Combined Modality Therapy, Adrenocortical carcinoma, Humans, Mitotane, Survivors, Neoplasm Metastasis, Aged, Endocrine and Autonomic Systems, business.industry, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for > 24 months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n = 57) or cytotoxic polychemotherapy plus/minus mitotane (PC ± M) (n = 11). The second-line therapy was M (n = 2) or PC ± M (n = 41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC ± M for 19/32 responders (59.4%). PRs were observed within 6 months of starting M or PC ± M in 76.9 and 94.7% of responses, respectively, within 6 months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC ± M. All PRs (but one) occurred within 1 year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6 months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1 year should be questioned in future randomized trials.
Published: 2017

48. Successful response to pegylated interferon alpha in a patient with recurrent paraganglioma

Author: Gerlinde Averous, Rossella Libé, Anne Paule Gimenez-Roqueplo, Laurence Kessler, Nelly Burnichon, Thibault Bahougne, Nassim Dali-Youcef, Eric Baudin, Alessio Imperiale, Catherine Roy, Hervé Lang, Gérard Chabrier, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), 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), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rare Adrenal Cancer Network COMETE/ Centre Expert National COMETE/Cancer de la surrénale [Paris] (CENC), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), and DALI-YOUCEF, Nassim
Subjects: Cancer Research, business.industry, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Alpha (ethology), 030209 endocrinology & metabolism, medicine.disease, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Text mining, Oncology, Paraganglioma, Pegylated interferon, 030220 oncology & carcinogenesis, Cancer research, Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; No abstract available
Published: 2017

49. Assessment of VAV2 expression refines prognostic prediction in adrenocortical carcinoma

Author: Carmen Ruggiero, Esther Korpershoek, Iuliu Sbiera, Guido Fadda, Hester Ettaieb, Jérôme Bertherat, Felix Beuschlein, Mabrouka Doghman-Bouguerra, Massimo Mannelli, Martin Reincke, Gabriella Nesi, Martin Fassnacht, Ronald R. de Krijger, Guillaume Assié, Silviu Sbiera, Bruno Ragazzon, Natalie Rogowski-Lehmann, Harm R. Haak, Rossella Libé, Barbara Altieri, Enzo Lalli, Marco Volante, Massimo Terzolo, Michaela Luconi, Mauro Papotti, Giuseppe Reimondo, Pathology, Promovendi PHPC, Health Services Research, Interne Geneeskunde, and RS: CAPHRI - R1 - Ageing and Long-Term Care
Subjects: 0301 basic medicine, Male, Internationality, Endocrinology, Diabetes and Metabolism, Biopsy, Clinical Biochemistry, Kaplan-Meier Estimate, medical, Biochemistry, Metastasis, Cohort Studies, 0302 clinical medicine, Endocrinology, Adrenocortical Carcinoma, Needle, Adrenocortical carcinoma, GENE-EXPRESSION, Tumor, Biopsy, Needle, PROLIFERATION, Middle Aged, Prognosis, TUMORS, CANCER, Combined Modality Therapy, Immunohistochemistry, GENOMIC CHARACTERIZATION, Diabetes and Metabolism, Multicenter Study, Europe, Treatment Outcome, Local, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, Context (language use), Malignancy, CLASSIFICATION, VALIDATION, Disease-Free Survival, 03 medical and health sciences, Text mining, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, Journal Article, medicine, Adrenal Cortex Neoplasms, Aged, Analysis of Variance, Humans, Multivariate Analysis, Neoplasm Recurrence, Local, Proto-Oncogene Proteins c-vav, Survival Analysis, Endocrine system, RECURRENCE, Biochemistry, medical, business.industry, Biochemistry (medical), Cancer, medicine.disease, 030104 developmental biology, Neoplasm Recurrence, MARKER, business, Biomarkers, HELSINKI SCORE
Abstract: Context Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has a major prognostic role in localized ACC after complete resection, but its estimates may suffer from considerable intra- and interobserver variability. VAV2 overexpression induced by increased Steroidogenic Factor-1 dosage is an essential factor driving ACC tumor cell invasion. Objective To assess the prognostic role of VAV2 expression in ACC by investigation of a large cohort of patients. Design, Setting, and Participants A total of 171 ACC cases (157 primary tumors, six local recurrences, eight metastases) from seven European Network for the Study of Adrenal Tumors centers were studied. Outcome Measurements H-scores were generated to quantify VAV2 expression. VAV2 expression was divided into two categories: low (H-score, Results VAV2 expression and Ki67 LI were significantly correlated with each other and with PFS and OS. Heterogeneity of VAV2 expression inside the same tumor was very low. Combined assessment of VAV2 expression and Ki67 LI improved patient stratification to low-risk and high-risk groups. Conclusion Combined assessment of Ki67 LI and VAV2 expression improves prognostic prediction in ACC.
Published: 2017

50. Macronodular Adrenal Hyperplasia due to Mutations in an Armadillo Repeat Containing 5 (ARMC5) Gene: A Clinical and Genetic Investigation

Author: Constantine A. Stratakis, Jérôme Bertherat, Stéphanie Espiard, Ninet Sinaii, Eva Szarek, Guillaume Assié, Bruno Ragazzon, Rossella Libé, Giampaolo Trivellin, Fabio R. Faucz, Ludivine Drougat, Maya Lodish, Annabel Berthon, and Mihail Zilbermint
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, DNA Mutational Analysis, Clinical Biochemistry, Mutation, Missense, Context (language use), Biology, Biochemistry, Germline, Cohort Studies, Cushing syndrome, symbols.namesake, Endocrinology, Germline mutation, Gene Frequency, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Cushing Syndrome, Hydrocortisone, Armadillo Domain Proteins, Sanger sequencing, JCEM Online: Advances in Genetics, Tumor Suppressor Proteins, Adrenalectomy, Biochemistry (medical), Middle Aged, medicine.disease, Molecular biology, Macronodular Adrenal Hyperplasia, symbols, Female, medicine.drug
Abstract: Inactivating germline mutations of the probable tumor suppressor gene, armadillo repeat containing 5 (ARMC5), have recently been identified as a genetic cause of macronodular adrenal hyperplasia (MAH).We searched for ARMC5 mutations in a large cohort of patients with MAH. The clinical phenotype of patients with and without ARMC5 mutations was compared.Blood DNA from 34 MAH patients was genotyped using Sanger sequencing. Diurnal serum cortisol measurements, plasma ACTH levels, urinary steroids, 6-day Liddle's test, adrenal computed tomography, and weight of adrenal glands at adrenalectomy were assessed.Germline ARMC5 mutations were found in 15 of 34 patients (44.1%). In silico analysis of the mutations indicated that seven (20.6%) predicted major implications for gene function. Late-night cortisol levels were higher in patients with ARMC5-damaging mutations compared with those without and/or with nonpathogenic mutations (14.5 ± 5.6 vs 6.7 ± 4.3, P.001). All patients carrying a pathogenic ARMC5 mutation had clinical Cushing's syndrome (seven of seven, 100%) compared with 14 of 27 (52%) of those without or with mutations that were predicted to be benign (P = .029). Repeated-measures analysis showed overall higher urinary 17-hydroxycorticosteroids and free cortisol values in the patients with ARMC5-damaging mutations during the 6-day Liddle's test (P = .0002).ARMC5 mutations are implicated in clinically severe Cushing's syndrome associated with MAH. Knowledge of a patient's ARMC5 status has important clinical implications for the diagnosis of Cushing's syndrome and genetic counseling of patients and their families.
Published: 2014

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