Objectives Introduction. The TCGA project identified four distinct prognostic groups of endometrial carcinoma (EC) based on molecular alterations among which two are correlated with an intermediate prognosis: the MisMatch Repair deficient (MMRd) and the No Specific Molecular Profile (NSMP) groups. NSMP represents a heterogenous subset of patients frequently harboring CTNNB1 alterations and presenting distinctive clinicopathologic features comparing with the CTNNB1 non mutant ones. miRNAs are oncological key players that have not been integrated with the TCGA EC classification. The study aimed to evaluate the miRNA expression profile in EC to identify potential novel biomarkers of diagnosis and prognosis.

Methods We analyzed miRNA expression in 72 ECs specimens previously classified as MMRd (31) and NSMP (41), including 15 with CTNNB1 mutations. In the discovery step, miRNA expression profile was evaluated in 30 cases through TaqMan Advanced miRNA arrays. Subsequently, in the validation step, four miRNAs were analyzed in the total cohort of ECs by specific miRNA Assays.

Results Comparison of CTNNB1 mutant versus non-mutant ECs (irrespective of MMRd/NSMP status) in the discovery cohort showed 39 differentially expressed miRNAs. The top deregulated 4 miRNAs (miR-187, miR-325, miR-499a-3p and 5p) were further validated in 72 ECs. miR-499a-3p and miR-499a-5p maintained the statistical significance showing higher expression in CTNNB1 mutant ECs (p<0.0001, for both). Furthermore, miR-499a expression was able to identify EC subgroups with longer recurrence free survival.

Conclusions Conclusion. miR-499a may be a useful biomarker and could be integrated in the current TGCA classification scheme to better stratify EC patients