Pathological analysis for premalignant lesions of colon cancer

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It is widely believed that colorectal carcinogenesis is a representative multistep tumorigenesis with events of genetic alterations. Aberrant crypt foci (ACF) recognized in the surface of cancer-predisposed colons of rodents have been regarded as early-appearing preneoplastic lesions. However, it is not clear that such lesions are truly precancerous lesions for colorectal cancers in rodents. Recently, we have identified β-catenin-accumulated crypts (BCAC) in colonic mucosa at the early stages of colon carcinogenesis.In this project, we performed further analyses of BCAC in rodents. We demonstrated that alterations in Wnt signaling pathway result in the formation of BCAC, and BCAC play an important role during early stages of colon carcinogenesis. Our results provide additional evidences that BCAC are premalignant lesions of colon cancer in rodents. We also showed that BCAC are reliable biomarkers for colon carcinogenesis. In addition, we searched for the similar dysplastic lesions as BCAC in human colon. We investigated a large number of histological sections from human colons. However, such lesions confirmed in rodents have not yet identified in human colonic mucosa. Now, we are going on further analyses to find out BCAC in human colon. We determined mutation spectrum of APC gene in small human colonic polyps and got some interesting results. Although the results are preliminary, we believe that such data provide important clue to understand the premalignancy of colon cancer in humans as well as rodents.