Genetic alterations in normal epithelium of colorectal cancer patients may be a useful indicator for subsequent metachronous tumor development.

Abstract

We attempted to identify areas of microsatellite alterations specific to histologically normal colorectal epithelium and to clarify the correlations among those molecular events and clinicopathologic features. We conducted a prospective observation study on 51 colorectal cancer patients. Preoperative blood and microdissected histologically normal colorectal epithelium and neoplastic tissues were collected. Microsatellite analyses with seven microsatellite loci were performed to examine the genetic potential of individual tumors and histologically normal colorectal epithelium. In the sporadic colorectal cancer group, p53 LOH in the neoplastic epithelium had a significant correlation with the maximum tumor diameter and the preoperative serum cancer antigen 19-9 level, but not with the depth of invasion of the primary tumor. Among the patients who had p53 LOH in the histologically normal colorectal epithelium, four additional tumors were discovered within 30 months after curative surgery. For those patients, microsatellite alterations in normal colorectal epithelium were more sensitive than tumor markers. For accurate LOH analysis, nonmalignant lymphocytes from blood should be used as the appropriate normal DNA sample. Focusing on the identification of high-risk patients for microsatellite alterations in histologically normal colorectal epithelium can be a useful indicator of subsequent metachronous tumor development after colorectal surgery. For accurate LOH analysis, nonmalignant lymphocytes from blood should be used as the appropriate normal DNA sample. Focusing on the identification of high-risk patients for microsatellite alterations in histologically normal colorectal epithelium can be a useful indicator of subsequent metachronous tumor development after colorectal surgery.