MICROSATELLITE INSTABILITY IN COLORECTAL ADENOMAS

Background & Aims: Microsatellite instability in apparently sporadic, predominantly right-sided colon cancers seems to be the result of an a cquired, rather than germline, genetic change that impairs mismatch re pair. The timing of this change with respect to the adenoma-carcinoma sequence has not been determined. The aim of this study was to evaluat e colonic adenomatous polyps for microsatellite instability to determi ne whether instability reflects an early genetic change in colonic neo plasia. Methods: Ninety-three sporadic colonic adenomas (44 right-side d and 49 left-sided) from 48 individuals were evaluated for microsatel lite instability with a set of 10 polymerase chain reaction primer set s. Results: Eighty percent of adenomatous polyps showed no instability . Ninety-eight percent showed instability with <30% of primer sets. As ide from one right-sided adenoma with 78% instability, there was no le vel of instability with a higher proportion of right-sided than left-s ided adenomas. Conclusions: Colonic adenomas show far less microsatell ite instability than carcinomas, and the marked right-sided predominan ce of instability observed in colon cancers was not observed. Instabil ity is usually not an early event in the development of colonic neopla sia. A distinct pathway to sporadic colorectal cancer initiated by mis match repair deficiency, although not excluded, is not suggested by th ese data.