Body Mass Index Associations Including Mismatch Repair Protein Expression in 1061 Endometrial Carcinomas
Amy S Joehlin-Price, Carmen M Perrino, Julie A Stephens, David E Cohn, Adrian A Suarez. Ohio State University Wexner Medical Center, Columbus, OH
Background: Obesity is a risk factor for endometrial carcinoma (EC). Body mass index (BMI) may be used to estimate the estrogen milieu that supports many EC, given adipose tissue production of estrone. Recent research indicates that estrogen may play a role in mismatch repair protein (MMR) expression maintenance in benign endometria and EC. While other clinicopathological features have consistently correlated with obesity, no clear association between BMI and MMR has emerged from recent series of EC. MMR immunohistochemistry (IHC) done in all hysterectomies with EC at our institution allows thorough analysis of MMR associations, now with more than double the cases we have previously analyzed.
Design: MLH1, PMS2, MSH2 and MSH6 on 1061 consecutive hysterectomy specimens with EC were classified as present or absent. Clinical databases were used to extract BMI data at the time of surgery. Relationships between MMR IHC, BMI, age, stage, and tumor type were explored.
Results: Women <50 years constituted 14% of the cases, had a significantly higher BMI (n=149, median BMI=39.2, range 17.8-89.7) than women ≥50 years (n=912, median BMI=34.9, range 14.2-82.4), p<0.001, and 135 (90.6%) of their tumors were type 1. Regardless of age, when separated by tumor type, more type 1 patients were obese (BMI ≥30) than type 2 patients, p<0.001. Additionally, type 1 tumors had a significantly lower stage than did type 2 tumors, p<0.001. MMR protein loss occurred at the same rate between type 1 and type 2 tumors, but obese patients had a lower MMR protein loss overall than under, normal, or overweight patients, p=0.004. In the <50 age group, BMI was significantly lower in patients who lost MSH2 or MSH6 individually, compared to those who retained expression, p=0.002 and 0.004 respectively. Similarly, obese patients <50 years old had a lower rate of MSH2 or MSH6 loss, p<0.001 and p=0.003. Women with loss of MLH1 (n=176) and/or PMS2 (n=191) were older than women with both proteins present (both p<0.001), and women with absent MSH2 (n=21) and/or MSH6 (n=50) were younger than women with both proteins present, p=0.007 and p<0.001, respectively.
Conclusions: BMI showed multiple significant associations. Higher BMI was seen in premenopausal women and in type 1 tumors. Overall, a higher BMI correlated with normal MMR supporting a possible role for estrogens in the maintenance of DNA repair in EC. These findings indicate particular BMI significance on MSH2 and MSH6 expression in obese women <50 years with EC.
Category: Gynecologic & Obstetrics
Monday, March 4, 2013 8:15 AM
Proffered Papers: Section E, Monday Morning