The Clinicopathological Significance and Prognostic Value of Androgen Receptor in Endometrial Carcinoma: A Meta-Analysis

Abstract

BackgroundThe role of androgen receptor (AR) in evaluating the prognosis of patients with endometrial cancer (EC) remains controversial. Here, we performed a meta-analysis to assess whether AR expression improves EC survival outcomes.MethodsWe searched related articles published before August 2021 in PubMed, EMBASE, and Web of Science. The association between AR expression and patient prognosis was estimated with hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs). The review is registered on PROSPERO, registration number: CRD42021268591.ResultsTen studies including 1,485 patients were enrolled in the meta-analysis. The results showed that AR expression in EC tissues was associated with a better survival in crude analyses (HR = 1.63, 95% CI = 1.32–2.02, P < 0.001). However, no significant relation was found after the adjustment of the confounding factors (HR = 1.68, 95% CI = 0.75–3.75, P = 0.205). In subgroup analyses, grade 1–2 disease, stage I–II disease, negative lymph node status, and lack of the lymphovascular invasion were more common in AR-positive groups (OR = 0.47, 0.48, 0.37, and 0.57; 95% CI = 0.45–0.62, 0.35–0.65, 0.24–0.56, and 0.37–0.89). Furthermore, AR expression was more common in endometrioid cancers (OR = 2.39, 95% CI = 1.79–3.20).ConclusionsAR expression is significantly associated favorable characteristics including low-grade disease, early-stage disease, negative lymph node status, and lack of the lymphovascular invasion and a specific histology—endometrioid cancer. However, AR is not an independent prognostic factor.

Circulating adrenal 11-oxygenated androgens are associated with clinical outcome in endometrial cancer

“…In addition to their aromatization to estrogens in multiple sites including adipose and uterine tissues ( 8 – 11 ), androgens and AR signaling pathway may play different roles in EC ( 12 – 14 ). Both oncogenic and tumor suppressive roles have been reported along with variable AR expression levels depending on the stage of disease ( 15 , 16 ). In EC cell models, evidence suggests interference with the progestin signaling, promotion of cell proliferation and drug resistance, although with inconsistent results ( 17 – 20 ).…”

Androgen Signaling in Uterine Diseases: New Insights and New Targets

“…However, enzalutamide increased tumor invasion and metastasis in advanced tumors [ 105 ]. A number of studies showed that AR expression was significantly increased in type I EC and was associated with favorable prognostic factors such as early stage of cancer, low grade, lymph node negativity, and reduced tumor recurrence rate [ 106 , 107 , 108 ]. Besides, decreased AR expression has been reported to lead to methylation of the MLH1 gene, which, in turn, causes mismatch repair (MMR) deficiency and promotes endometrial carcinogenesis [ 109 ].…”