Prognostic impact of molecular subgroups in grade 3 endometrioid endometrial carcinoma: a single cohort study in Northern China

Background: To evaluate the prognostic impact of the molecular classification of grade 3 endometrioid endometrial carcinoma (G3-EEC) and its correlation with clinicopathological factors. Methods: 137 patients with G3-EEC were enrolled and molecularly classified using Sanger sequencing in exons 9–14 of the polymerase epsilon (POLE) gene and immunohistochemistry (IHC) staining for p53, MLH1 (mutL homolog 1), PMS2 (PMS1 homolog 2), MSH2 (mutS homolog 2) and MSH6 (mutS homolog 6). The Kaplan-Meier method and Cox regression were used for survival analysis, and the chi-square and Fisher’s exact tests were used for comparisons between categorical data. Results: POLE hotspot mutations (POLEmut group) were identified in seven tumors (5.1%); 46 (33.6%) tumors showed deficient mismatch repair (dMMR group); 22 (16.1%) showed abnormal p53 staining (p53abn group); and 58 (42.3%) were classified as nonspecific molecular profiles (NSMP group). The remaining four patients (2.9%) were grouped as multi-classifiers. The median follow-up was 45.2 months (range: 6‒128 months), with an overall survival (OS) rate of 84.6% (116/137) and a progression-free survival (PFS) rate of 81.7% (112/137). There was no significant difference in the molecular subgroups with OS and PFS (p = 0.05 and p = 0.162, respectively). The prognosis was most favorable in the POLEmut, intermediate in the dMMR and NSMP, worst in the p53abn group, and unclear in the multi-classifier group. Multivariate analysis showed that the International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO 2009 and FIGO 2023) and lymphovascular space invasion were significant independent prognostic factors in OS and PFS (p < 0.05). Myometrial invasion, bizarre atypia, and peritumoral lymphocytes showed significant differences among the molecular groups (p = 0.026, p < 0.001 and p = 0.001, respectively). Conclusions: Our study demonstrated the prognostic value of the molecular classification of G3-EEC. The biological behavior of the multi-classifier group remains undefined.

Prognostic impact; Molecular classification; Grade 3 endometrioid endometrial carcinoma

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