Molecular Profiling and Treatment Outcomes in Uterine Serous Carcinoma: Prognostic Role of Estrogen Receptor Expression

TL;DR

This study explores how estrogen receptor expression affects survival in uterine serous carcinoma, a rare and aggressive cancer.

Contribution

The study identifies estrogen receptor (ER) expression as a potential prognostic marker for improved disease-free survival in uterine serous carcinoma.

Findings

ER-positive tumors were associated with improved disease-free survival after initial treatment.

TP53 mutations were common in 88% of cases, and HER2 amplification was observed in 18%.

Advanced stage remained an independent predictor of worse overall survival.

Abstract

Uterine serous carcinoma is a rare and aggressive form of endometrial cancer often diagnosed at an advanced stage. In this retrospective single-institution study, we analyzed the clinical characteristics, treatments, molecular markers, and outcomes of 83 patients. Most tumors showed TP53 mutations, while estrogen receptor (ER) expression and HER2 amplification were also observed. ER-positive tumors were associated with improved disease-free survival after initial treatment, although no association was observed with progression-free or overall survival. These results highlight the biological heterogeneity of uterine serous carcinoma and the potential prognostic role of ER expression in this population.

Background: Uterine serous carcinoma (USC) represents a rare but aggressive subtype of endometrial cancer, accounting for a disproportionate number of disease-related deaths. Although molecular classification has improved risk stratification, prognostic heterogeneity highlights the need for new prognostic markers. Methods: We retrospectively analyzed 83 patients with USC treated at our institution between 1 January 2015 and 31 December 2023. Clinicopathological characteristics, treatment strategies, molecular biomarkers accessed by immunohistology (TP53, ER, PR, HER2, and MMR status), and survival outcomes were collected. Patients were first staged by FIGO 2009 and retrospectively reclassified by FIGO 2023. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) were assessed using Kaplan–Meier and Cox regression analyses. Results: The majority of patients were presented with advanced disease (FIGO stage IIIC-IV). TP53 mutations were found in 88% of cases, HER2 amplification in 18%, and ER expression in 57.8%. ER-positive patients showed significantly improved DFS in the adjuvant setting compared with ER-negative patients, whereas no significant associations were observed for first-line PFS or OS in multivariable analyses. HER2 amplification was not associated with inferior survival in our cohort. The advanced stage remained an independent predictor of worse OS. Conclusions: USC is a biologically heterogeneous disease, and its treatment should be guided by its molecular profile. ER expression identifies a subset of patients with improved DFS, suggesting potential prognostic relevance in this high-risk histology.

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