Obesity correlates to the microsatellite instability of endometrial cancer: A retrospective observational study

To investigate the relationship between obesity and Microsatellite Instability (MSI) in endometrial cancer (EC), determine which mismatch repair (MMR) protein loss is influenced by obesity, and assess the correlation between BMI and MSI probability.

This retrospective cohort study included 89 endometrial cancer patients treated at the Gynaecologic oncology unit of the University of Campania "Luigi Vanvitelli" from August 2023 to October 2024, and stratified by BMI: normal weight (n = 26), overweight (n = 31), obese (n = 26), and severely obese (n = 6). Microsatellite instability (MSI) was determined through immunohistochemical assessment of mismatch repair (MMR) protein expression: MLH1, PMS2, MSH2, and MSH6. Tumors were considered MSI if at least one of the four MMR proteins showed loss of expression. Univariate and multivariate logistic regression models were constructed to evaluate the correlation between BMI and MSI RESULTS: 89 patients were enrolled. Obese and severely obese groups showed significantly higher MSI rates (50 % each) compared to normoweight (12 %) and overweight (29 %) groups (P = .013). MLH1 and PMS2 loss of expression were significantly higher in obese and severely obese women (MLH1: P = .003; PMS2: P = .014). Univariate logistic regression showed a significant positive correlation between BMI and MSI (OR 1.02, 95 % CI 1.01-1.04, P = .007). In multivariate analysis, adjusting for grading, stage, histotype, and age, BMI maintained a significant positive correlation with MSI (OR 1.02, 95 % CI 1.01-1.04, P = .048).

This study demonstrates a significant association between obesity and MSI in EC, particularly affecting MLH1 and PMS2 expression. The findings suggest that obesity may contribute to EC development also through MMR deficiency.