The Impact of Androgen Receptor Expression on Endometrial Carcinoma Recurrence and Survival

Abstract

Endometrial carcinomas (ECs) are the most common gynecologic cancers in the western world. The impact of androgen receptor (AR) on clinicopathologic parameters of EC is not well studied. The aim of our study is to assess the role of AR expression in ECs and correlate its expression with estrogen (ER) and progesterone (PR). A retrospective review of 261 EC was conducted. H&E slides were reviewed and clinicopathologic parameters were analyzed. Immunohistochemical stains for AR, ER, and PR were performed on a tissue microarray. The hormonal expression was evaluated and the data were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. Patients' age ranged from 31 to 91 (median=65 y). Type I EC included 202 endometrioid and 7 mucinous carcinoma, whereas type II included 34 serous, 16 carcinosarcoma, and 2 clear cell carcinoma. Although not significant, AR expression showed more frequent association with type I EC, early tumor stage (I-II), and low FIGO grade (1-2) EC. AR expression significantly correlated with absence of lymphovascular invasion (P=0.041) and decreased LN involvement (P=0.048). Patients with AR expression showed increased disease-free survival (208 vs. 165 mo, P=0.008) and late disease recurrence (P=0.009). AR expression had a positive significant correlation with PR (P<0.001) and ER (P=0.037) expression. AR might play a role as a prognostic marker for ECs.

Androgen receptor as a prognostic biomarker and therapeutic target in uterine leiomyosarcoma

“…Also, AR expression was more common in early stage, lower tumor differentiation, and type 1 endometrial cancer [ 21 ]. Furthermore, it was significantly related with no lymph-vascular invasion, LNM, higher DFS, and delayed recurrence event in endometrial cancer [ 21 ].…”

“…Also, AR expression was more common in early stage, lower tumor differentiation, and type 1 endometrial cancer [ 21 ]. Furthermore, it was significantly related with no lymph-vascular invasion, LNM, higher DFS, and delayed recurrence event in endometrial cancer [ 21 ]. As with previous studies in endometrial cancer, the expression of AR was related to the lower rate of recurrence and death events in our study [ 21 ].…”

“…Furthermore, it was significantly related with no lymph-vascular invasion, LNM, higher DFS, and delayed recurrence event in endometrial cancer [ 21 ]. As with previous studies in endometrial cancer, the expression of AR was related to the lower rate of recurrence and death events in our study [ 21 ]. Leitao et al [ 13 ] reported better DFS in patients with no PR and AR expression [ 19 ].…”

“…In contrast to many previous studies on hormone receptors, few studies have further reached its attention to recognize androgen receptor (AR) as a potential prognostic marker in uterine leiomyosarcoma, although AR shares a common deoxyribonucleic acid (DNA)/ligand-binding domain with molecular structure and is evolutionarily closely related with estrogen receptor (ER)/progesterone receptor (PR) [ 18 19 ]. Based on observing an indolent disease character, better differentiated histologic feature, and more favorable survival outcome in endometrial cancer and stromal sarcoma with AR expression [ 20 21 ], we hypothesized that it may also be associated with a better disease extent and survival outcome in uterine leiomyosarcoma. Thus, we comprehensively investigated the significance of all of the hormone receptors, including AR, in clinicopathological characters and survival outcomes in uterine leiomyosarcoma.…”

Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma

“…Women with elevated circulating androgens have a 2-3 fold increased risk of developing endometrial cancer and administration of synthetic androgens to mice results in endometrial hyperplasia [2]. In humans, multiple studies observed increased AR protein expression in endometrial hyperplasia and cancer, with low-grade endometrioid, or type-I carcinomas more commonly positive than higher grade histologies [3][4][5][6]. Furthermore, positive AR expression has been associated with improved prognosis relative to AR-negative tumors [3,6].…”