Immunohistochemical evaluation of androgen receptor expression in endometrial carcinoma and its clinicopathological significance

Abstract Background Endometrial carcinoma (EC) is a leading gynecological malignancy predominantly driven by hormonal imbalances. While the roles of estrogen and progesterone are well established, the influence of androgenic signaling, specifically through the androgen receptor, remains an underexplored diagnostic dimension. This study aims to evaluate the immunohistochemical (IHC) expression of the androgen receptor (AR) in EC tissue samples and correlate its presence with key clinicopathological parameters. Methods A retrospective cohort study was conducted utilizing 40 formalin-fixed, paraffin-embedded (FFPE) tissue specimens from patients diagnosed with EC who had undergone total hysterectomies. Cases were histologically categorized according to World Health Organization (WHO) criteria into endometrioid endometrial carcinoma (EEC), n = 32 and serous endometrial carcinoma, n = 8, and classified by the International Federation of Gynecology and Obstetrics (FIGO) for staging and grading. IHC staining was performed to evaluate nuclear AR expression, defined as positive when > 10% of neoplastic cells exhibited distinct nuclear staining. Data were statistically analyzed to identify associations between AR status and patient age, histological subtype, tumor grade, and stage. Results Distinct nuclear AR positivity was observed in 50% (20 of 40) of the total cohort. Expression was exclusively restricted to EEC (62.5% positive), whereas all serous carcinomas lacked expression entirely ( P = 0.002). Notably, positive receptor expression demonstrated a strong inverse relationship with advanced FIGO stage and high tumor grade. Immunoreactivity was significantly enriched in early-stage disease (62.1% in Stages I and II versus 18.2% in Stage III; P = 0.013) and low-grade tumors (76.0% in Grades 1 and 2 versus 6.7% in Grade 3; P < 0.001). Patient age at diagnosis yielded no statistically significant correlation with expression status ( P = 0.206). Conclusion The AR is frequently expressed in low-grade, early-stage EEC, suggesting that AR may be associated with well-differentiated tumors and favorable clinicopathological parameters. The integration of AR immunohistochemistry into routine pathology panels could serve as a hypothesis-generating foundation for future clinical trials investigating targeted antiandrogen therapies.