Validation of comprehensive genomic profiling for prognostic and potential therapeutic molecular classification of endometrial cancer

作者：Brian M. Slomovitz, Natalie A. Danziger, Júlia C.F. Quintanilha, Andrew D. Kelly, Gerald Li, Vivek Podder, Douglas I. Lin, Ryon P. Graf, Julia Andrea Elvin, Thomas J. Herzog · 发表于：International Journal of Gynecological Cancer · 年份：2025 · DOI：10.1016/j.ijgc.2025.102107 · 被引用次数：6 · 研究领域：Endometrial and Cervical Cancer Treatments、Gynecological conditions and treatments、14-3-3 protein interactions

OBJECTIVE: We sought to validate the prognostic utility of comprehensive genomic profiling (CGP)-based molecular stratification for patients with endometrial carcinoma and to assess co-occurring biomarkers across subtypes. METHODS: This study included patients from a de-identified nationwide (US-based) endometrial cancer clinicogenomic database who underwent CGP testing as part of routine care. Molecular subtypes were classified as POLE mutated (POLEmut), MSI-H, TP53 mutated (TP53mut), and no specific molecular profile (NSMP). Time to next treatment and overall survival were compared between molecular subtypes, with multivariable Cox models adjusted for relevant covariables. RESULTS: Of 1,139 evaluated patients with advanced or recurrent endometrial carcinoma, the prevalence of the 4 molecular subtypes was 1% POLEmut, 22% high microsatellite instability, 47% TP53mut, and 31% NSMP. Compared with NSMP patients, POLEmut patients had numerically more favorable time to next treatment (HR 0.50, 95% CI 0.21 to 1.21) and overall survival (HR 0.52, 95% CI 0.17 to 1.66). High microsatellite instability patients had similar time to next treatment (HR 1.08, 95% CI 0.89 to 1.30) and overall survival (HR 0.91, 95% CI 0.71 to 1.19) relative to NSMP patients. TP53mut patients had the least favorable outcomes for time to next treatment (compared with NSMP, HR 1.39, 95% CI 1.19 to 1.62) and overall survival (HR 2.15, 95% CI 1.77 to 2.61). In multivariable analysis, TP53mut status was associate...