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 Osorio, Andreas D. Hartkopf, Angela Brooks-Wilson, Anna DeFazio, Anna Fischer, Arndt Hartmann, Brenda Y. Hernandez, Bryan M. McCauley, Chloe KarpinskyjChristiani B. de Sousa, Claus Høgdall, Daniel G. Tiezzi, Esther Herpel, Florin Andrei Taran, Francesmary Modugno, Gary Keeney, Gregg Nelson, Helen Steed, Honglin Song, Hugh Luk, Javier Benitez, Jennifer Alsop, Jennifer M. Koziak, Jenny Lester, Joseph H. Rothstein, Jurandyr M. de Andrade, Lene Lundvall, Luis Paz-Ares, Luis Robles-Díaz, Lynne R. Wilkens, Maria J. Garcia, Maria P. Intermaggio, Marie Lyne Alcaraz, Mary A. Brett, Matthias W. Beckmann, Mercedes Jimenez-Linan, Michael Anglesio, Michael E. Carney, Michael Schneider, Nadia Traficante, Nadja Pejovic, Naveena Singh, Nhu Le, Peter Sinn, Prafull Ghatage, Ramona Erber, Robert Edwards, Robert Vierkant, Roberta B. Ness, Samuel Leung, Sandra Orsulic, Sara Y. Brucker, Scott H. Kaufmann, Sian Fereday, Simon Gayther, Stacey J. Winham, Stefan Kommoss, Tanja Pejovic, Teri A. Longacre, Valerie McGuire, Valerie Rhenius, Weiva Sieh, Yurii B. Shvetsov, Alice S. Whittemore, Annette Staebler, Beth Y. Karlan, Cristina Rodriguez-Antona, David D. Bowtell, Ellen L. Goode, Estrid Høgdall, Francisco J. Candido 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)793-802
Number of pages10
JournalBritish Journal of Cancer
Volume123
Issue number5
DOIs
StatePublished - Sep 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Martins, F. C., Couturier, D. L., Paterson, A., Karnezis, A. N., Chow, C., Nazeran, T. M., Odunsi, A., Gentry-Maharaj, A., Vrvilo, A., Hein, A., Talhouk, A., Osorio, A., Hartkopf, A. D., Brooks-Wilson, A., DeFazio, A., Fischer, A., Hartmann, A., Hernandez, B. Y., McCauley, B. M., ... Brenton, J. D. (2020). Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium. British Journal of Cancer, 123(5), 793-802. https://doi.org/10.1038/s41416-020-0900-0