Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Martins FC, Couturier DL, Paterson A, Karnezis AN, Chow C, Nazeran TM, Odunsi A, Gentry-Maharaj A, Vrvilo A, Hein A, Talhouk A, Osorio A, Hartkopf AD, Brooks-Wilson A, DeFazio A, Fischer A, Hartmann A, Hernandez BY, McCauley BM, Karpinskyj C, de Sousa CB, Høgdall C, Tiezzi DG, Herpel E, Taran FA, Modugno F, Keeney G, Nelson G, Steed H, Song H, Luk H, Benitez J, Alsop J, Koziak JM, Lester J, Rothstein JH, de Andrade JM, Lundvall L, Paz-Ares L, Robles-Díaz L, Wilkens LR, Garcia MJ, Intermaggio MP, Alcaraz ML, Brett MA, Beckmann M, Jimenez-Linan M, Anglesio M, Carney ME, Schneider M, Traficante N, Pejovic N, Singh N, Le N, Sinn P, Ghatage P, Erber R, Edwards R, Vierkant R, Ness RB, Leung S, Orsulic S, Brucker SY, Kaufmann SH, Fereday S, Gayther S, Winham SJ, Kommoss S, Pejovic T, Longacre TA, McGuire V, Rhenius V, Sieh W, Shvetsov YB, Whittemore AS, Staebler A, Karlan BY, Rodriguez-Antona C, Bowtell DD, Goode EL, Høgdall E, Candido dos Reis FJ, Gronwald J, Chang-Claude J, Moysich KB, Kelemen LE, Cook LS, Goodman MT, Fasching P, Crawford R, Deen S, Menon U, Huntsman DG, Köbel M, Ramus SJ, Pharoah PD, Brenton JD (2020)


Publication Type: Journal article

Publication year: 2020

Journal

DOI: 10.1038/s41416-020-0900-0

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.

Authors with CRIS profile

Involved external institutions

University of New South Wales (UNSW) AU Australia (AU) University of Hawaiʻi at Mānoa US United States (USA) (US) Peter MacCallum Cancer Centre AU Australia (AU) Mayo Clinic US United States (USA) (US) Strangeways Research Laboratory GB United Kingdom (GB) Cedars-Sinai Medical Center US United States (USA) (US) Universitätsklinikum Tübingen DE Germany (DE) Stanford University US United States (USA) (US) University of British Columbia CA Canada (CA) Roswell Park Cancer Institute US United States (USA) (US) University of Calgary CA Canada (CA) Addenbrooke's Hospital GB United Kingdom (GB) University of Cambridge GB United Kingdom (GB) UC Davis Medical Center US United States (USA) (US) BC Cancer Research Centre CA Canada (CA) University College London (UCL) GB United Kingdom (GB) University of São Paulo / Universidade de São Paulo (USP) BR Brazil (BR) Rigshospitalet DK Denmark (DK) British Columbia Cancer Agency CA Canada (CA) Alberta Health Services (AHS) CA Canada (CA) University of Sydney (USYD) AU Australia (AU) Royal Alexandra Hospital (RAH) CA Canada (CA) Oregon Health and Science University (OSHU) US United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) ES Spain (ES) University of Pittsburgh US United States (USA) (US) Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg DE Germany (DE) Hospital Universitario 12 de Octubre ES Spain (ES) Icahn School of Medicine at Mount Sinai US United States (USA) (US) University of Hawaii (U.H.) US United States (USA) (US) Saint Louis University (SLU) US United States (USA) (US) The University of Melbourne AU Australia (AU) Barts Health NHS Trust GB United Kingdom (GB) Universitätsklinikum Heidelberg DE Germany (DE) University of Texas Health Science Center at Houston (UTHealth) US United States (USA) (US) Nottingham University Hospitals GB United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) PL Poland (PL) Kræftens Bekæmpelse DK Denmark (DK) Medical University of South Carolina (MUSC) US United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) University of New Mexico (UNM) / Universidad de Nuevo México US United States (USA) (US)

How to cite

APA:

Martins, F.C., Couturier, D.L., Paterson, A., Karnezis, A.N., Chow, C., Nazeran, T.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. https://doi.org/10.1038/s41416-020-0900-0

MLA:

Martins, Filipe Correia, et al. "Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium." British Journal of Cancer (2020).

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