Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival |
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Authors: | A M Kamal J N Bulmer S B DeCruze H F Stringfellow P Martin-Hirsch D K Hapangama |
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Affiliation: | 1.Department of Women''s and Children''s Health, Institute of Translational Medicine, University of Liverpool, Liverpool L8 7SS, UK;2.The National Center for Early Detection of Cancer, Oncology Teaching Hospital, Baghdad Medical City, Baghdad, Iraq;3.Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK;4.Liverpool Women''s Hospital NHS Foundation Trust, Liverpool L8 7SS, UK;5.Lancashire Teaching Hospital NHS Trust, Lancaster University, Preston PR2 9HT UK |
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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 (ERα and ERβ) 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 ERα (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 ERβ (P<0.035) compared with LGEC, whilst maintaining weak to moderate ERα. 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 ERα and ERβ may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC. |
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Keywords: | androgen receptor (AR), endometrial cancer, postmenopausal endometrium, metastatic lesions, ERβ , ERα , PR, outcome |
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