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

Filipe Correia Martins(University of Cambridge), Dominique‐Laurent Couturier(University of Cambridge), Anna Paterson(Addenbrooke's Hospital), Anthony N. Karnezis(University of California Davis Medical Center), Christine Chow(Vancouver Coastal Health), Tayyebeh M. Nazeran, Adekunle Odunsi(Roswell Park Comprehensive Cancer Center), Aleksandra Gentry‐Maharaj(MRC Clinical Trials Unit at UCL), Aleksandra Vrvilo(Oregon Health & Science University), Alexander Hein(Universitätsklinikum Erlangen), Aline Talhouk(University of British Columbia), Ana Osório(Instituto de Salud Carlos III), Andreas D. Hartkopf(University Children's Hospital Tübingen), Angela Brooks‐Wilson(Canada's Michael Smith Genome Sciences Centre), Anna DeFazio(The University of Sydney), Anna Fischer(University Children's Hospital Tübingen), Arndt Hartmann(Universitätsklinikum Erlangen), Brenda Y. Hernandez(University of Hawaiʻi at Mānoa), Bryan M. McCauley(Mayo Clinic in Florida), Chloe Karpinskyj(MRC Clinical Trials Unit at UCL), Christiani Bisinoto de Sousa(Universidade de São Paulo), Claus Høgdall(Rigshospitalet), Daniel Guimarães Tiezzi(Universidade de São Paulo), Esther Herpel(Heidelberg University), Florin‐Andrei Taran(University Children's Hospital Tübingen), Francesmary Modugno(University of Pittsburgh), Gary L. Keeney(Mayo Clinic in Florida), Gregg Nelson(University of Calgary), Helen Steed(Royal Alexandra Hospital), Honglin Song(University of Cambridge), Hugh Luk(University of Hawaiʻi at Mānoa), Javier Benı́tez(Instituto de Salud Carlos III), Jennifer Alsop(University of Cambridge), Jennifer M. Koziak(Alberta Health Services), Jenny Lester(Cedars-Sinai Medical Center), Joseph H. Rothstein(Icahn School of Medicine at Mount Sinai), Jurandyr Moreira de Andrade(Universidade de São Paulo), Lene Lundvall(Rigshospitalet), Luis Paz‐Ares(Cancer Clinic), Luis A. Díaz‐Robles(Hospital Universitario 12 De Octubre), Lynne R. Wilkens(University of Hawaiʻi at Mānoa), María J. García(Instituto de Salud Carlos III), Maria P. Intermaggio(UNSW Sydney), Marie‐Lyne Alcaraz(University of Cambridge), Mary Anne Brett(University of Calgary), Matthias W. Beckmann(Universitätsklinikum Erlangen), Mercedes Jimenez‐Liñan(Addenbrooke's Hospital), Michael S. Anglesio(Vancouver Coastal Health), Michael E. Carney(University of Hawaiʻi at Mānoa), Michael Schneider(Universitätsklinikum Erlangen), Nadia Traficante(The University of Melbourne), Nadja Pejovic(Saint Louis University), Naveena Singh(National Health Service), Nhu D. Le(BC Cancer Agency), Hans‐Peter Sinn(Heidelberg University), Prafull Ghatage(University of Calgary), Ramona Erber(Universitätsklinikum Erlangen), Robert P. Edwards(University of Pittsburgh), Robert A. Vierkant(Mayo Clinic in Florida), Roberta B. Ness(The University of Texas Health Science Center at Houston), Samuel Leung(Vancouver Coastal Health), Sandra Oršulić(Cedars-Sinai Medical Center), Sara Y. Brucker(University Children's Hospital Tübingen), Scott H. Kaufmann(Mayo Clinic in Florida), Sián Fereday(The University of Melbourne), Simon A. Gayther(Cedars-Sinai Medical Center), Stacey J. Winham(Mayo Clinic in Florida), Stefan Kommoss(University Children's Hospital Tübingen), Tanja Pejović(Oregon Health & Science University), Teri A. Longacre(Stanford University), Valerie McGuire(Stanford University), Valerie Rhenius(University of Cambridge), Weiva Sieh(Icahn School of Medicine at Mount Sinai), Yurii B. Shvetsov(University of Hawaiʻi at Mānoa), Alice S. Whittemore(Stanford University), Annette Staebler(University Children's Hospital Tübingen), Beth Y. Karlan(Cedars-Sinai Medical Center), Cristina Rodríguez‐Antona(Spanish National Cancer Research Centre), David D.L. Bowtell(Garvan Institute of Medical Research), Ellen L. Goode(Mayo Clinic in Florida), Estrid Høgdall(University of Copenhagen), Francisco José Cândido dos Reis(Universidade de São Paulo), Jacek Gronwald(International Hereditary Cancer Center), Jenny Chang‐Claude(Universität Hamburg), Kirsten B. Moysich(Roswell Park Comprehensive Cancer Center), Linda E. Kelemen(Medical University of South Carolina), Linda S. Cook(University of New Mexico), Marc T. Goodman(Cedars-Sinai Medical Center), Peter A. Fasching(University of California, Los Angeles), Robin Crawford(Addenbrooke's Hospital), Suha Deen(Nottingham University Hospitals NHS Trust), Usha Menon(MRC Clinical Trials Unit at UCL), David G. Huntsman(Vancouver Coastal Health), Martin Köbel(University of Calgary), Susan J. Ramus(Garvan Institute of Medical Research), Paul D.P. Pharoah(Cancer Research UK Cambridge Center), James D. Brenton(Cancer Research UK)
British Journal of Cancer
June 17, 2020
10.1038/s41416-020-0900-0
Cited by 68Open Access
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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.

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