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

Accepted version
Peer-reviewed

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Authors

Martins, Filipe Correia 
Couturier, Dominique-Laurent 
Paterson, Anna 
Karnezis, Anthony N 
Chow, Christine 

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.

Description

Keywords

Adenocarcinoma, Clear Cell, Age Factors, Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Cohort Studies, Down-Regulation, Female, Gene Knockout Techniques, Humans, Middle Aged, Neoplasm Staging, Ovarian Neoplasms, PTEN Phosphohydrolase, Prospective Studies, Receptors, Androgen, Receptors, Estrogen, Receptors, Progesterone, Tissue Array Analysis, Tumor Suppressor Proteins

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

123

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cancer Research UK (C14303/A17197)
Cancer Research UK (22905)
Cancer Research UK (15601)
Cancer Research Uk (None)
Cancer Research UK (24267)
Cancer Research UK (22905)
Cancer Research UK (15601)