Mismatch repair protein expression in 1049 endometrial carcinomas, associations with body mass index, and other clinicopathologic variables

• We analyzed data from 1049 hysterectomy specimens with endometrial carcinoma.
• BMI and MMR correlation is explained by young women with MSH2/MSH6 loss and low BMI.
• Higher BMI correlated with lower stage and grade of endometrial carcinoma; lower BMI correlated with increased MMR protein loss.

ObjectiveLinks between obesity, with its attendant estrogen abnormalities, and the endometrial carcinoma (EC) DNA Mismatch Repair Protein (MMR) system have recently been proposed. We investigated relationships between body mass index (BMI) and clinicopathological correlates including MMR expression in a large single institution EC cohort.MethodsClinical and pathological databases from 2007 to 2012 were used to identify consecutive hysterectomy specimens with EC. Univariate and multivariate analyses were used to explore relationships between BMI, age, stage, tumor type and immunohistochemical results for MLH1, PMS2, MSH2 and MSH6.Results1049 EC were identified. Overall, BMI was higher amongst women with normal MMR (p = 0.002). However, when stratified by age and specific MMR, statistically significant differences localized exclusively to women < 50 years old with loss of MSH2 and/or MSH6 (p = 0.003 and p = 0.005 respectively). Higher BMI correlated with endometrioid FIGO 1 and 2 tumors (p < 0.001) and with stage 1a (p < 0.001). Conversely, MMR abnormalities did not show significant associations with stage (p = 0.302) or histologic grade (p = 0.097).ConclusionsBMI showed statistically significant associations with MMR expression, tumor grade and stage amongst 1049 consecutive EC. Obesity correlates with lower grade and stage EC. A link between BMI and maintenance of the MMR system is not supported by our data because the only statistically significant association occurred in women < 50 years old with MSH2 and/or MSH6 abnormalities where Lynch syndrome related cases are expected to cluster.