Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium
Creators: name: Martins, Filipe Correia
name: Couturier, Dominique-Laurent
name: Paterson, Anna
name: Karnezis, Anthony N.
name: Chow, Christine
name: Nazeran, Tayyebeh M.
name: Odunsi, Adekunle
name: Gentry-Maharaj, Aleksandra
name: Vrvilo, Aleksandra
name: Hein, Alexander
name: Talhouk, Aline
name: Osorio, Ana
name: Hartkopf, Andreas D.
name: Brooks-Wilson, Angela
name: DeFazio, Anna
name: Fischer, Anna
name: Hartmann, Arndt
name: Hernandez, Brenda Y.
name: McCauley, Bryan M.
name: Karpinskyj, Chloe
name: De Sousa, Christiani B.
name: Høgdall, Claus
name: Tiezzi, Daniel G.
name: Herpel, Esther
name: Taran, Florin Andrei
name: Modugno, Francesmary
name: Keeney, Gary
name: Nelson, Gregg
name: Steed, Helen
name: Song, Honglin
name: Luk, Hugh
name: Benitez, Javier
name: Alsop, Jennifer
name: Koziak, Jennifer M.
name: Lester, Jenny
name: Rothstein, Joseph H.
name: De Andrade, Jurandyr M.
name: Lundvall, Lene
name: Paz-Ares, Luis
name: Robles-Díaz, Luis
name: Wilkens, Lynne R.
name: Garcia, Maria J.
name: Intermaggio, Maria P.
name: Alcaraz, Marie-Lyne
name: Brett, Mary A.
name: Beckmann, Matthias W.
name: Jimenez-Linan, Mercedes
name: Anglesio, Michael
name: Carney, Michael E.
name: Schneider, Michael
name: Traficante, Nadia
name: Pejovic, Nadja
name: Singh, Naveena
name: Le, Nhu
name: Sinn, Peter
name: Ghatage, Prafull
name: Erber, Ramona
name: Edwards, Robert
name: Vierkant, Robert
name: Ness, Roberta B.
name: Leung, Samuel
name: Orsulic, Sandra
name: Brucker, Sara Y.
name: Kaufmann, Scott H.
name: Fereday, Sian
name: Gayther, Simon
name: Winham, Stacey J.
name: Kommoss, Stefan
name: Pejovic, Tanja
name: Longacre, Teri A.
name: McGuire, Valerie
name: Rhenius, Valerie
name: Sieh, Weiva
name: Shvetsov, Yurii B.
name: Whittemore, Alice S.
name: Staebler, Annette
name: Karlan, Beth Y.
name: Rodriguez-Antona, Cristina
name: Bowtell, David D.
name: Goode, Ellen L.
name: Høgdall, Estrid
name: Candido Dos Reis, Francisco J.
name: Gronwald, Jacek
name: Chang-Claude, Jenny
name: Moysich, Kirsten B.
name: Kelemen, Linda E.
name: Cook, Linda S.
name: Goodman, Marc T.
name: Fasching, Peter A.
name: Crawford, Robin
name: Deen, Suha
name: Menon, Usha
name: Huntsman, David G.
name: Köbel, Martin
name: Ramus, Susan J.
name: Pharoah, Paul D. P.
name: Brenton, James D.
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Article
/692/4017
/692/4028/67/1517/1709
article

description: 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 &lt; 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.