Background & aims: Microsatellite instability in apparently sporadic, predominantly right-sided colon cancers seems to be the result of an acquired, rather than germline, genetic change that impairs mismatch repair. The timing of this change with respect to the adenomacarcinoma sequence has not been determined. The aim of this study was to evaluate colonic adenomatous polyps for microsatellite instability to determine whether instability reflects an early genetic change in colonic neoplasia.
Methods: Ninety-three sporadic colonic adenomas (44 right-sided and 49 left-sided) from 48 individuals were evaluated for microsatellite instability with a set of 10 polymerase chain reaction primer sets.
Results: Eighty percent of adenomatous polyps showed no instability. Ninety-eight percent showed instability with <30% of primer sets. Aside from one right-sided adenoma with 78% instability, there was no level of instability with a higher proportion of right-sided than left-sided adenomas.
Conclusions: Colonic adenomas show far less microsatellite instability than carcinomas, and the marked right-sided predominance of instability observed in colon cancers was not observed. Instability is usually not an early event in the development of colonic neoplasia. A distinct pathway to sporadic colorectal cancer initiated by mismatch repair deficiency, although not excluded, is not suggested by these data.