Purpose: The aim of this study was to elucidate pathways of carcinogenesis in the colon and rectum by investigating Ki-ras point mutation in different types of colorectal carcinomas in the early stage.
Methods: We analyzed rates of Ki-ras codon 12 mutations in 34 small, polypoid-type carcinomas (Tis or T1), 21 superficial-type carcinomas (Tis or T1), and 42 advanced carcinomas (T2, T3, and T4).
Results: Frequency of Ki-ras mutations in superficial-type carcinomas was 14.3 percent (3/21), which was significantly lower than 50 percent (17/34) in small polypoid carcinomas and 40.5 percent (17/42) in advanced carcinomas. These data suggest that another pathway of colorectal carcinogenesis that does not involve Ki-ras point mutation might exist. Among the 17 small polypoid carcinomas with Ki-ras point mutation in which both adenomatous and carcinomatous tissue were examined, 12 showed a mutation of the same type in both carcinomatous and adenomatous tissues. In two cases, mutation was present only in carcinomatous tissue and not in adenomatous tissue; in the other three cases, Ki-ras point mutation was present only in adenomatous tissue but not in carcinomatous tissue.
Conclusions: These data suggest that carcinoma in a small polypoid lesion does not always develop from pre-existing adenoma with Ki-ras point mutation; in a small number of the polypoid-type early carcinomas, polyclonal composition concerning the Ki-ras gene may exist.