Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium
Authors: Martins Filipe Correia , Couturier Dominique-Laurent , Paterson Anna , Karnezis Anthony N. , Chow Christine , Nazeran Tayyebeh M. , Odunsi Adekunle , Gentry-Maharaj Aleksandra , Vrvilo Aleksandra , Hein Alexander , Talhouk Aline , Osorio Ana , Hartkopf Andreas D. , Brooks-Wilson Angela , DeFazio Anna , Fischer Anna , Hartmann Arndt , Hernandez Brenda Y. , McCauley Bryan M. , Karpinskyj Chloe , de Sousa Christiani B. , Høgdall Claus , Tiezzi Daniel G. , Herpel Esther , Taran Florin Andrei , Modugno Francesmary , Keeney Gary , Nelson Gregg , Steed Helen , Song Honglin , Luk Hugh , Benitez Javier , Alsop Jennifer , Koziak Jennifer M. , Lester Jenny , Rothstein Joseph H. , de Andrade Jurandyr M. , Lundvall Lene , Paz-Ares Luis , Robles-Díaz Luis , Wilkens Lynne R. , Garcia Maria J. , Intermaggio Maria P. , Alcaraz Marie-Lyne , Brett Mary A. , Beckmann Matthias W. , Jimenez-Linan Mercedes , Anglesio Michael , Carney Michael E. , Schneider Michael , Traficante Nadia , Pejovic Nadja , Singh Naveena , Le Nhu , Sinn Peter , Ghatage Prafull , Erber Ramona , Edwards Robert , Vierkant Robert , Ness Roberta B. , Leung Samuel , Orsulic Sandra , Brucker Sara Y. , Kaufmann Scott H. , Fereday Sian , Gayther Simon , Winham Stacey J. , Kommoss Stefan , Pejovic Tanja , Longacre Teri A. , McGuire Valerie , Rhenius Valerie , Sieh Weiva , Shvetsov Yurii B. , Whittemore Alice S. , Staebler Annette , Karlan Beth Y. , Rodriguez-Antona Cristina , Bowtell David D. , Goode Ellen L. , Høgdall Estrid , Candido dos Reis Francisco J. , Gronwald Jacek , Chang-Claude Jenny , Moysich Kirsten B. , Kelemen Linda E. , Cook Linda S. , Goodman Marc T. , Fasching Peter A. , Crawford Robin , Deen Suha , Menon Usha , Huntsman David G. , Köbel Martin , Ramus Susan J. , Pharoah Paul D. P. , Brenton James D. 
Published: June 2020

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.