Abstract
PurposeThe expression and involvement of estrogen (ER) and progesterone receptor (PR) is extensively studied in endometrial cancer. Androgen receptor (AR) is a hormone receptor less studied in female cancers, and we here aim to investigate the expression level of AR in endometrial cancer precursor lesions, primary tumors and metastases, and its potential as therapeutic target.ResultsExpression of AR was observed in 93% of hyperplasias, but only in 41% of non-endometrioid tumors. Compared to estrogen and progesterone receptor AR is more commonly expressed in metastatic lesions, and AR status is discordant in primary and metastatic lesions in a large proportion of cases. AR protein level was significantly associated with survival (P < 0.001), and a calculated AR to ERα ratio identified a subgroup of patients with particular poor outcome. The anti-androgen enzalutamide may have a growth inhibitory effect in endometrial cancer cells based on experiments with primary endometrial tumor cells.MATERIALS AND METHODS718 primary endometrial cancers and 298 metastatic lesions (from 142 patients) were investigated for expression of AR in relation to survival, clinical and histopathological data. Protein levels were investigated by immunohistochemistry and reverse phase protein array; mRNA levels by DNA oligonucleotide microarray. The effect of androgen stimulation and inhibition was tested on primary endometrial tumor cells.ConclusionsA large proportion of metastatic endometrial cancer lesions express AR, which may be a potential target in these patients. Treatment targeting AR may be of particular benefit in patients with high AR levels compared to ERα levels.
Highlights
Endometrial cancer is the most common gynecological malignancy in the Western countries [1]
Androgen receptor (AR) protein level was significantly associated with survival (P < 0.001), and a calculated AR to ERα ratio identified a subgroup of patients with particular poor outcome
The anti-androgen enzalutamide may have a growth inhibitory effect in endometrial cancer cells based on experiments with primary endometrial tumor cells
Summary
Endometrial cancer is the most common gynecological malignancy in the Western countries [1]. Little progress has been made in development of treatment options over the past decades. This, combined with a rising incidence, has resulted in an increased number of deaths caused by the disease [2]. Patients with localized disease have a good prognosis, prognosis is poor for patients with recurrence or metastatic disease at diagnosis and treatment options are few [3]. To improve treatment of this patient group, both the identification of new treatment targets, and identification of potent biomarkers to aid patient stratification are vital. Endometrial cancers have been divided into two groups.
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