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Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival

Lookup NU author(s): Dr Judith Bulmer

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background: Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described.Methods: The expression pattern and prognostic value of AR in relation to oestrogen (ER alpha and ER beta) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n = 85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR.Results: Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P<0.001) and ERa (P = 0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P<0.0001), PR (P<0.0001) and ERb (P<0.035) compared with LGEC, whilst maintaining weak to moderate ER alpha. Unlike PR, AR expression in metastatic lesions was significantly (P = 0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P<0.0001, P<0.0001, respectively).Conclusions: Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ER alpha and ER beta may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC.


Publication metadata

Author(s): Kamal AM, Bulmer JN, DeCruze SB, Stringfellow HF, Martin-Hirsch P, Hapangama DK

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2016

Volume: 114

Issue: 6

Pages: 688-696

Print publication date: 15/03/2016

Online publication date: 01/03/2016

Acceptance date: 22/12/2015

Date deposited: 16/05/2016

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/bjc.2016.16

DOI: 10.1038/bjc.2016.16


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