Molecular genetic changes in benign colorectal tumors synchronous with microsatellite unstable carcinomas do not support a field defect.

BACKGROUND: A colorectal cancer may develop through a particular molecular genetic pathway, raising the question of whether the particular molecular changes are random, or are unique to the particular segment of colon. We wanted to determine whether molecular changes found within a colorectal cancer might also be detected in separate adenomas and polyps removed from the same area of colon at surgery. Microsatellite instability was chosen as a marker for a pathway of colon carcinogenesis.
METHODS: We studied a total of 46 primary colorectal cancers with microsatellite instability and 77 synchronous adenomas and polyps. All tumors were evaluated for microsatellite instability, BRAF and KRAS mutations, and methylation using standard polymerase chain reaction based methods.
RESULTS: Forty-nine benign tumors did not follow a pathway similar to that of their 31 synchronous primary cancers. For two distinct subsets of the microsatellite unstable colorectal cancers, those with acquired methylation and BRAF mutation, and those without methylation suggestive of an underlying germ line mutation, the molecular changes in the majority of their synchronous benign tumors were different from the colorectal cancer.
CONCLUSIONS: These differences suggest a stochastic process within the colon regarding the particular molecular carcinogenic pathways followed by the synchronous tumors, rather than a 'field defect' within the colon segments. Variability in molecular findings was present for colorectal cancers arising from acquired methylation, as well as those cancers suggestive of a germ line origin.