Lower Incidence of K‐ras Codon 12 Mutation in Flat Colorectal Adenomas than in Polypoid Adenomas

In order to clarify genetic changes in flat adenomas, K‐ras codon 12 point mutations were examined in 56 flat adenomas, 81 polypoid adenomas and 42 cancers of colon and rectum. The mutation frequency in flat adenomas was 23% (13/56), significantly lower than that in polypoid adenomas (67%: 54/81) and cancers (76%: 32/42). Even mildly dysplastic adenomas or small (less than 5 mm) adenomas showed higher mutation incidence in polypoid type (62%, 57%) than in flat type (23%, 19%). Among flat adenomas, flat elevated lesions exhibited relatively higher mutation frequency than completely flat or depressed ones. As for cancers, 14 tumors (33%) contained mutations only in a minor tumor cell population, indicating that these mutations occur at a late stage of tumorigenesis. These results suggest that the adenoma‐carcinoma sequence through flat adenomas may he different from that through polypoid adenomas, and genetic changes may be heterogeneous in colorectal carcinogenesis.