Evaluating the prognostic value of estrogen receptor status in stage III MMR-proficient endometrial cancer: real-world data from an Asian population.

To evaluate the prognostic value of estrogen receptor (ER) expression in mismatch repair-proficient (MMRp) stage III endometrial cancer (EC) in an Asian cohort using an immunohistochemistry (IHC) - based molecular classification, we retrospectively analyzed patients with stage III EC classified by IHC into three molecular subtypes: mismatch repair-deficient (MMRd), TP53-mutant, and MMRp. The MMRp group was further stratified by ER expression (10% cutoff) into ER-positive and ER-negative subgroups, yielding four molecular subtypes. Clinicopathological features and survival outcomes were compared. Ninety-five patients were included: 7 (7.4%) with MMRp ER-negative, 34 (35.8%) with MMRp ER-positive, 27 (28.4%) with MMRd, and 27 (28.4%) with TP53-mutant tumors. With a median follow-up of 61 months, progression-free survival (PFS) and cancer-specific survival (CSS) differed significantly across four IHC-based subtypes (log-rank P = 0.0013 and P<0.0001, respectively). In multivariate Firth's penalized Cox regression, MMRp ER-negative status was an independent predictor of poor PFS (HR 4.91; 95% CI, 1.43-15.80) and CSS (HR 7.44; 95% CI, 1.85-30.80), independent of histologic grade. Even within low-risk MMRp endometrioid grade 1-2 tumors, ER-negativity identified a high-risk subset (12.1%, 4/33). To our knowledge, this is among the first studies to evaluate the prognostic relevance of ER expression in stage III MMRp EC in an Asian cohort using a pragmatic IHC-based approach. Low ER expression identified a distinct high-risk subgroup whose outcomes approached those of TP53-mutant tumors.