ECE2009 Clinical Highlights Hot topics: Clinical (5 abstracts)
ESE Young Investigator Award
Guillaume Assié 1, , Aurélien de Reyniès 6, , David Rickman 6, , Frédérique Tissier 1, , Lionel Groussin 1, , Fernande René-Corail 1, , Bertrand Dousset 4, , Xavier Bertagna 1, , Eric Clauser 1, & Jérôme Bertherat 1,
1Department Endocrinology Metabolism Cancer, Institut Cochin, Université Paris Descartes, INSERM U567, CNRS UMR8104 Paris, France; 2Department of Endocrinology, Assistance Publique Hopitaux de Paris, Cochin Hospital, Paris, France; 3Department of Pathology, Assistance Publique Hopitaux de Paris, Cochin Hospital, Paris, France; 4Department of Digestive and Endocrine Surgery, Assistance Publique Hopitaux de Paris, Cochin Hospital, Paris, France; 5Department of Oncogenetics, Assistance Publique Hopitaux de Paris, Cochin Hospital, Paris, France; 6Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France; 7Adrenal Cancer Newtork-COMETE, INCA, Paris, France.
Diagnosing malignancy and assessing the prognosis of adrenocortical tumors is challenging. The aim is to identify molecular predictors of malignancy and of survival.
Patients and methods: Of 153 unilateral adrenocortical tumors were studied by microarray (n=92) or RT-qPCR (n=148). A 2-gene predictor of malignancy was built using the disease-free survival as the end-point in a training cohort (n=47), then validated in an independent validation cohort (n=104). The best candidate genes were selected using Cox models, and the best gene combination was validated using the log-rank test. Similarly, for malignant tumors, a 2-gene predictor of survival was built using the overall survival as the end-point in a training cohort (n=23), then tested in an independent validation cohort (n=35).
Results: Unsupervised clustering analysis discriminated the malignant and benign tumors, and identified two groups of malignant tumors with different outcome. Predictors based on gene expression levels were determined. The substraction DGL7-PINK1 was the best predictor of disease free survival (log-rank P≈10–12), could overcome the uncertainties of intermediate pathological Weiss scores, and remained significant after adjustment to the Weiss score (P<1.3×10-2). Among the malignant tumors, the substraction BUB1B-PINK1 was the best predictor of overall survival (P<2×10-6), and remained significant after adjusting for MacFarlane staging (P<0.005).
Conclusion: Gene expression analysis unravels two distinct groups of adrenocortical carcinomas. The molecular predictors of malignancy and of survival are reliable and provide valuable independent information in addition to pathology and tumor staging. These original tools should provide important improvements for adrenal tumors management.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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