Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium
Filipe Correia Martins, Dominique‐Laurent Couturier, Anna Paterson, Anthony N. Karnezis, Christine Chow, Tayyebeh M. Nazeran, Adekunle Odunsi, Aleksandra Gentry‐Maharaj, Aleksandra Vrvilo, Alexander Hein, Aline Talhouk, Ana Osório, Andreas D. Hartkopf, Angela Brooks‐Wilson, Anna DeFazio, Anna Fischer, Arndt Hartmann, Brenda Y. Hernandez, Bryan M. McCauley, Chloe Karpinskyj, Christiani Bisinoto de Sousa, Claus Høgdall, Daniel Guimarães Tiezzi, Esther Herpel, Florin‐Andrei Taran, Francesmary Modugno, Gary L. Keeney, Gregg Nelson, Helen Steed, Honglin Song, Hugh Luk, Javier Benı́tez, Jennifer Alsop, Jennifer M. Koziak, Jenny Lester, Joseph H. Rothstein, Jurandyr Moreira de Andrade, Lene Lundvall, Luis Paz‐Ares, Luis A. Díaz‐Robles, Lynne R. Wilkens, María J. García, Maria P. Intermaggio, Marie‐Lyne Alcaraz, Mary Anne Brett, Matthias W. Beckmann, Mercedes Jimenez‐Liñan, Michael S. Anglesio, Michael E. Carney, Michael Schneider, Nadia Traficante, Nadja Pejovic, Naveena Singh, Nhu D. Le, Hans‐Peter Sinn, Prafull Ghatage, Ramona Erber, Robert P. Edwards, Robert A. Vierkant, Roberta B. Ness, Samuel Leung, Sandra Oršulić, Sara Y. Brucker, Scott H. Kaufmann, Sián Fereday, Simon A. Gayther, Stacey J. Winham, Stefan Kommoss, Tanja Pejović, Teri A. Longacre, Valerie McGuire, Valerie Rhenius, Weiva Sieh, Yurii B. Shvetsov, Alice S. Whittemore, Annette Staebler, Beth Y. Karlan, Cristina Rodríguez‐Antona, David D.L. Bowtell, Ellen L. Goode, Estrid Høgdall, Francisco José Cândido dos Reis, Jacek Gronwald, Jenny Chang‐Claude, Kirsten B. Moysich, Linda E. Kelemen, Linda S. Cook, Marc T. Goodman, Peter A. Fasching, Robin Crawford, Suha Deen, Usha Menon, David G. Huntsman, Martin Köbel, Susan J. Ramus, Paul D.P. Pharoah, James D. Brenton
Abstract
BACKGROUND: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. METHODS: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests. RESULTS: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). CONCLUSIONS: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.