Prevalence of Mismatch Repair Deficiency and Its Association with Histopathological Parameters in Endometrial Cancer: A Prospective Cohort Study.

Mismatch repair deficiency (MMRd) is a critical biomarker in endometrial cancer (EC) for prognostication, Lynch syndrome screening, and immunotherapy eligibility. This study aimed to determine the prevalence of MMRd and its correlation with clinicopathological characteristics in EC. This prospective observational cohort included 93 patients with EC undergoing primary surgical treatment, managed as per the European Society of Gynaecological Oncology (ESGO) guidelines. MLH1, PMS2, MSH2, and MSH6 expression was assessed through immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded hysterectomy specimens. Associations between mismatch repair (MMR) status and histology, grade, lymphovascular space invasion (LVSI), myometrial invasion, FIGO 2023 stage, nodal status, recurrence, and survival were analyzed. The median age was 66 years. Most tumors were endometrioid (86%), 29% were grade 3, 45.2% showed deep myometrial invasion, and 23.7% had substantial LVSI. MMRd was identified in 41.9% of cases, with MLH1 and PMS2 loss being most frequent, and was significantly associated with endometrioid histology (p = 0.027) and deep myometrial invasion (p = 0.011). No significant correlations were found with grade, LVSI, FIGO stage, nodal involvement, recurrence, or overall survival. Routine MMR assessment may refine risk stratification and guide individualized treatment decisions.