Histotype and Grade Are of Prognostic Significance in the No Specific Molecular Profile Molecular Subtype of Endometrial Carcinoma But Not in POLEmut, MMRd, or p53abn Endometrial Carcinomas: Results From a 2478 Case Series and a Systematic Review of the Literature

Histotype and grade of endometrial carcinoma (EC) have been cornerstones of risk assessment, as both are known to be associated with differences in prognosis. The aim of this study was to analyze the prognostic significance of grade and histotype (comparing low-grade endometrioid, high-grade endometrioid, serous, and all others) within each EC molecular subtype, with further stratification by stage. A cohort of 2478 patients with EC were identified from our center. Disease-specific survival was compared for tumors of each molecular subtype after stratification of patients into 1 of 4 groups (low-grade endometrioid, high-grade endometrioid, serous, other). In addition, a systematic review of the literature was undertaken to identify all previous studies where the prognostic significance of grade and histotype within molecular subtypes was reported. Grade and histotype were not of prognostic significance in POLE mut or p53abn EC across all stages and when just considering stage I ECs. MMRd low-grade ECs were associated with a better prognosis; however, they were also associated with lower stage disease, and within stage I tumors, grade and histotype were not of prognostic significance. Grade and histotype were of prognostic significance in NSMP ECs, in all stages and in the subset of stage I tumors ( P <0.001 for both analyses). On a systematic review of the literature, we identified 7 studies; there was no prognostic significance of grade and histotype (comparing low-grade endometrioid, high-grade endometrioid and serous) in POLE mut, and p53abn EC, and no prognostic significance of grade and histotype independent of stage in MMRd. Histotype and grade are strongly associated with prognosis in NSMP EC, but not in other molecular subtypes.