Colorectal mucosal expression of MSH2 as a potential biomarker of risk for colorectal neoplasms.

To characterize the expression of the mismatch repair gene MSH2 in normal colorectal crypts in humans and assess parameters of its expression as a potential modifiable biomarker of risk for colorectal neoplasms, we conducted a pilot, colonoscopy-based case-control study (51 cases and 154 controls) of incident, sporadic colorectal adenoma. Biopsies of normal-appearing rectal, sigmoid, and ascending colon mucosa were procured, immunohistochemically processed for MSH2 protein, and analyzed using custom quantitative image analysis procedures. MSH2 expression in adenoma cases was lower than in controls by 49% (P = 0.01) and 23% (P = 0.06) in the ascending colon and rectum, respectively, but not in the sigmoid colon. MSH2 expression in the rectum was 39% (P = 0.04) higher in subjects who regularly took a nonsteroidal anti-inflammatory drug than in those who did not, and it tended to be lower in those with adenomas in the right colon and those who had an adenoma with more advanced characteristics. These preliminary data suggest that lower MSH2 expression in the normal colonic mucosa, at least in the ascending colon and rectum, may be associated with increased risk of incident, sporadic colorectal adenoma as well as with modifiable risk factors for colorectal neoplasms, thus supporting further investigation of MSH2 expression as a potential modifiable biomarker of risk for colorectal neoplasms.