The significance of microsatellite instability in predicting the development of metachronous multiple colorectal carcinomas in patients with nonfamilial colorectal carcinoma

Abstract

BACKGROUND. Patients with metachronous multiple colorectal carcinomas have been reported to have a higher frequency of a family history of colorectal carcinoma, associated colorectal adenomas, and extracolonic malignancies. These clinicopathologic factors also are considered to be related to the development of metachronous multiple colorectal carcinomas after surgery for colorectal carcinoma. In this article, the authors investigated whether genetic markers such as microsatellite instability (MSI) were helpful in predicting the development of metachronous multiple colorectal carcinomas. METHODS. Between 1990-1997, 312 colorectal carcinoma patients underwent yearly surveillance colonoscopy after surgery. Among these patients, there were 19 with nonfamilial colorectal carcinoma in whom metachronous multiple colorectal carcinomas were diagnosed during the yearly surveillance colonoscopy. A control group was comprised of 28 patients who did not demonstrate either synchronous or metachronous carcinomas over a period of ≥5 years. Six microsatellite markers (D2S123, D3S1029, D3S1611, TP53, Mfd26, and Mfd36) were used to determine MSI by polymerase chain reaction. RESULTS. The frequency of MSI positive cases was significantly higher in patients with sporadic metachronous multiple colorectal carcinomas than in those with a single carcinoma (17/19 [89%] vs. 4/28 [14%]; P < 0.0001). In tumors occurring in the distal colon and rectum, the percentage of MSI positive carcinomas was significantly higher in the patients with metachronous multiple carcinomas than in those with a single carcinoma (13/15 [87%] vs. 0/19 [0%]; P < 0.0001). No such difference was observed in the proximal colon. CONCLUSIONS. Based on the findings of the current study, the analysis of MSI in sporadic carcinomas of the distal colon and rectum may be helpful in predicting the development of metachronous multiple colorectal carcinomas.