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

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 α and ER β) 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 ER α ( 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 ER β ( P<0.035) compared with LGEC, whilst maintaining weak to moderate ER α. 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 α and ER β may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC.