# Association Between MMR Status and Prognostic Pathological Factors in Endometrioid Endometrial Cancer—A Single-Center Retrospective Study

## TL;DR

This study explores how mismatch repair status affects the prognosis of endometrioid endometrial cancer, finding that dMMR tumors are more likely to have advanced disease and lymphovascular invasion.

## Contribution

The study provides new evidence on the association between dMMR status and adverse prognostic features in endometrioid endometrial cancer.

## Key findings

- dMMR tumors were more likely to present with advanced FIGO stage III/IV disease.
- dMMR tumors showed a higher prevalence of lymphovascular space invasion.
- No significant differences were found in tumor grade or receptor positivity between dMMR and pMMR groups.

## Abstract

Clinical and pathological heterogeneity of endometrial carcinoma is not fully investigated, particularly in relation to mismatch repair (MMR) status. In practice, tumor profiles combining dMMR with adverse features may support therapy escalation, whereas favorable features support de-escalation. Identifying dMMR tumors has therapeutic relevance, guiding the consideration of immune checkpoint inhibitors. Previous studies have reported various findings regarding the impact of MMR deficiency, especially with respect to clinical progression of the disease, tumor grade, and the presence of adverse histopathological features such as lymphovascular space invasion (LVSI). By investigating these associations in our retrospective patient cohort, we aim to clarify the impact of MMR status on disease aggressiveness and to contribute evidence that may guide clinical decision-making. This study is centered on histopathological risk factors of endometrial cancer.

Background/Objectives: Prognostic assessment in endometrial cancer (EC) is based on clinical and pathological features such as histological type, FIGO stage, tumor grade, LVSI, P53 status, and hormone receptor expression. Recent molecular research has distinguished four EC subtypes, with MMR status (pMMR vs. dMMR) providing clinically relevant stratification due to its predictive value for immunotherapy. The present study aims to compare dMMR and pMMR tumors in terms of the prevalence of adverse histopathological prognostic factors. Methods: This retrospective study included 179 patients with endometrioid endometrial carcinoma (EEC) treated at the authors’ institution (1 January 2023–31 August 2025). Patients were classified by MMR status (pMMR vs. dMMR) based on immunohistochemistry, and clinicopathological variables, including FIGO stage, myometrial invasion depth, tumor grade, LVSI, ER/PR expression, and P53 status, were analyzed. Normality was assessed using the Shapiro–Wilk test. Categorical variables were tested with chi-square or Fisher’s exact tests, reporting odds ratios with 95% CI, while continuous variables were compared using the Mann–Whitney test and presented as median (IQR) with the Hodges–Lehmann difference and 95% CI. Multivariable logistic regression with Wald tests was performed. Results: dMMR tumors accounted for 29.05% of all cases. Patients in the dMMR group were significantly more likely to present with FIGO stage III/IV disease (p = 0.036) and to exhibit LVSI (p = 0.008). No differences were observed between the groups with respect to tumor grade, estrogen receptor positivity, progesterone receptor positivity, or the prevalence of deep myometrial invasion. The most frequent pattern of protein loss in the dMMR population was concurrent loss of MLH1 and PMS2. Conclusions: In the studied population, dMMR tumors more frequently exhibited adverse prognostic features of EC, such as advanced stage of disease and lymphovascular space invasion. This suggests the potential for effective immunotherapy in this patient group.