A possible multiclonal development in human colonic carcinomas

In order to define whether all colonic tumors develop from a single transformed cell, we compared two sites each in 40 early-stage colonic carcinomas by K-ras mutation and DNA ploidy pattern. These 40 colonic carcinomas consisted of 26 protruding-type carcinomas and 14 superficial-type carcinomas. The two sites were selected in every tumor tissue and then DNA ploidy pattern and occurrence of K-ras mutation were detected. In cases of "cancer in adenoma", we compared clonality between cancer cells and adenoma cells. In a cytofluorometrical study, it was shown that diploid patterns were predominantly seen in protruding-type carcinomas (76.9%), whereas many superficial-type carcinomas (64.3%) consisted of aneuploid cells. K-ras mutations were more frequently observed in protruding-type carcinomas: 42.3% in protruding-type compared to 21.4% in superficial-type carcinomas. These findings suggested that superficial-type carcinomas have a different mode of carcinogenesis from that of protruding-type carcinomas. Frequently, each pair of sites of the carcinoma tissue carried the same K-ras mutation, and DNA ploidy patterns were essentially the same. However, we encountered some cancers that showed different K-ras mutations in the cancer tissues. In particular, one case of cancer in adenoma demonstrated different K-ras mutations in the cancer and adenoma tissue. These findings suggest that most colonic cancers develop monoclonally, but there are a few cancers (fewer than 5%) that start multiclonally.