Body Mass Index Correlates with Mismatch Repair Protein Expression in Endometrial Carcinomas
Carmen M Perrino, Amy S Joehlin-Price, Alessandra C Schmitt, David E Cohn, Julie A Stephens, Adrian A Suarez. The Ohio State University, Columbus, OH
Background: Mismatch repair protein (MMR) immunohistochemistry (IHC) of endometrial carcinomas (EC) is routinely used to screen for Lynch syndrome at our institution. Body mass index (BMI) can be used to estimate the estrogen milieu because adipose tissue production of estrone. There is some evidence linking estrogen with MMR regulation in colorectal carcinomas (CRC) and similar mechanisms may be operative in EC.
Design: We retrospectively reviewed MMR IHC including MLH1, PMS2, MSH2 and MSH6 on 517 consecutive hysterectomy specimens with EC. Each IHC was classified as positive or negative. Equivocal IHC cases were resolved by staining sections of another block, two cases remained unresolved. Clinical databases were accessed to extract BMI data at the time of surgery. Relationships between MMR IHC, BMI, age and tumor type were explored.
Results: Women <50 years constituted 13% of the cases, had a significantly higher BMI (n=69, BMI=40.4 +/- 12.8) than women ≥50 years (n=448, BMI=36.4 +/- 9.95), p=0.013 and 60 (87%) of their tumors were type 1 (considered estrogen driven). Regardless of age, a significantly higher BMI was seen in 356 cases with normal MMR IHC (BMI=37.6 +/-10.5) when compared to 159 cases with any MMR absent on IHC (BMI=35.5 +/-10.2) p=0.027. When age was analyzed as a continuous variable: (1) women with absent MLH1 (n=116) and/or PMS2 (n=130) were significantly older than women with both proteins present (both p<0.001) and (2) women with absent MSH2 (n=12) and/or MS6 (n=29) were significantly younger than women with both proteins present (p=0.025 and p=0.002 respectively). A significant individual MMR loss-BMI association was found for MSH6 in women <50 with lower BMI correlating with negative MSH6 IHC (p=0.003).
Conclusions: BMI showed multiple statistically significant associations across our 517 hysterectomy cases. Overall, a higher BMI correlated with normal MMR indicating a possible role for estrogens in the maintenance of DNA repair in EC as has been suggested in CRC. These findings indicate particular BMI significance on MSH2 and/or MSH6 expression in women <50 years with EC.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 141, Wednesday Morning