# Clinicopathological Significance of Defective DNA Mismatch Repair in Endometrial Carcinoma: A Single-Center Study From Bahrain

## TL;DR

This study from Bahrain examines endometrial cancer, finding a high prevalence of MMR deficiency, which could impact treatment and screening strategies.

## Contribution

The study provides new insights into MMR deficiency prevalence and clinicopathological associations in endometrial carcinoma in Bahrain.

## Key findings

- Endometrioid carcinoma was the most common histologic subtype (73%).
- A significant proportion of cases showed MMR protein loss, with PMS2 and MLH1 being most affected.
- MMR deficiency was not significantly associated with patient age.

## Abstract

Introduction: Endometrial carcinoma, the most prevalent gynecologic malignancy in developed countries, represents a significant public health issue worldwide. DNA mismatch repair (dMMR) deficiency is an important molecular mechanism in endometrial carcinoma development, clinical course, and prognosis.

Aims and objectives: This study aimed to determine the incidence and histological subtypes of endometrial carcinoma among Bahraini women, evaluate the prevalence of MMR deficiency using immunohistochemistry in these patients and analyze the association between MMR deficiency and clinicopathological features, including potential links to Lynch syndrome.

Patients and methods: This single-center retrospective study included 115 endometrial carcinoma patients diagnosed between January 2020 to June 2023. Immunohistochemistry was used to assess the expression of the four main MMR proteins (MLH1, MSH2, MSH6, PMS2). Clinicopathological features and survival outcomes were compared between MMR-deficient and MMR-proficient tumors. Medical records of patients were retrieved from I-SEHA system. Statistical analysis was done using SPSS.

Results: The study included a wide age range of patients, with a mean age of 59.5 years. The majority were Bahraini nationals. Endometrioid carcinoma was the most common histologic subtype (73%), followed by serous carcinoma (8.7%). Most patients presented with early-stage disease (76.8% stage I), and 39.8% had low-grade tumors. Significant proportions of cases showed loss of expression of mismatch repair (MMR) proteins MLH1 (24.2%), PMS2 (25%), MSH6 (14.5%), and MSH2 (12.7%), without significant associations with age.

Conclusion: This study found endometrial cancer to be a significant health concern in Bahrain, with a relatively high prevalence and younger age of onset compared to global averages. The data shows a predominance of endometrioid subtype and higher-grade tumors. Notably, a substantial proportion exhibited MMR deficiency, an important biomarker. These findings suggest the need for enhanced screening, early detection, and tailored treatment approaches in Bahrain. Further research and robust national cancer registries are warranted to fully understand the underlying risk factors and guide evidence-based interventions to mitigate the burden of this disease.