KRAS gene mutations are more common in colorectal villous adenomas and in situ carcinomas than in carcinomas.

We have evaluated the frequency of KRAS gene mutations during the critical transition from villous adenoma to colorectal carcinoma to assess whether the adenomas contain a KRAS mutation more frequently than carcinomas. We analyzed sporadic villous and tubulovillous adenomas, in situ carcinomas, and primary colorectal carcinomas from multiple patients. The cancers were further evaluated for mucinous status and microsatellite instability. Standard PCR molecular techniques were used for KRAS and microsatellite analyses. A KRAS mutation was found in 61.9% of 134 adenomas, 67.8% of 84 in situ carcinomas, and just 31.6% of 171 carcinomas. Our study clearly demonstrates that tubulovillous and villous adenomas, as well as both the benign and malignant parts of in situ carcinomas, are statistically more likely to contain a somatic KRAS gene mutation than colorectal carcinomas. This difference is confined to the non-mucinous and the microsatellite stable tumors. Our data support the possibility that non-mucinous and microsatellite stable carcinomas with wild-type KRAS gene may have had a mutation in the KRAS gene during their earlier stages, with the mutation lost during further growth.