The prognostic potential of molecular subtypes including estrogen receptor status in endometrioid ovarian cancer.

Background: The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has been shown to be applicable to endometrioid ovarian cancer (ENOC), classifying tumors into four molecular subgroups: POLE mutated (POLEmut), mismatch repair deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP). However, the large NSMP subgroup in ENOC limits its clinical applicability. Incorporating estrogen receptor (ER) status has improved prognostic accuracy in NSMP endometrial cancer. Therefore, this study investigated the prognostic value of ER status in the molecular subgroups of ENOC.

Methods: In this multicenter, retrospective cohort study, paraffin-embedded tumor tissue from surgically treated ENOC patients (1994-2021) was used for molecular classification. ER status was determined by immunohistochemistry. Survival analysis was performed using the log-rank test and Cox proportional hazards model.

Results: Of the 167 included patients, 1.2 % had a POLEmut tumor, 6.6 % an MMRd tumor, 11.4 % a p53abn tumor, and 80.8 % an NSMP tumor. ER status was negative in 12 % of tumors, correlating with a significantly lower 10-year overall survival rate compared to ER-positive tumors (HR 3.51, 95 % CI 1.75-7.01, p < .001). No ER-negative tumors were found in the POLEmut and MMRd subgroups, and ER status was not prognostic in the p53abn subgroup. In the NSMP subgroup, 11.1 % of tumors were ER-negative, showing a worse 10-year overall survival rate (HR 3.92, 95 % CI 1.67-9.21, p = .002).

Conclusions: ER status improves prognostic stratification within the NSMP subgroup in ENOC, with ER-negative tumors associated with a worse prognosis. These findings may lead to more personalized treatment strategies for ENOC.