beta-catenin expression is altered in human colonic aberrant crypt foci

The aberrant expression of beta -catenin in colon tumors and the discovery of beta -catenin mutations in small adenomas suggest that alterations of be ta -catenin are early events in human colorectal carcinogenesis. Here, we d escribe the expression of beta -catenin in human aberrant crypt foci (ACF), the earliest identified neoplastic lesions in the colon. Paraffin-embedded sections of 94 ACF, 12 adenomas, and 10 carcinomas were evaluated for beta -catenin expression by immunohistochemistry. Normal colonic epithelial cel ls adjacent to these lesions showed strong membranous expression of beta -c atenin and lacked cytoplasmic and nuclear expression. Cytoplasmic expressio n of beta -catenin was seen in 25 of 46 ACF with dysplasia and in 2 of 48 A CF with atypia. In ACF with dysplasia, reduced membranous expression of bet a -catenin was associated with increased nuclear (P = 0.0013) and cytoplasm ic (P = 0.0247) expression. The membranous (P = 0.0003) expression of beta -catenin was reduced, and the cytoplasmic (P = 0.0016) and nuclear (P = 0.0 266) expressions increased in ACF according to their degree of dysplasia. L ikewise, membranous (P = 0.0007) expression of beta -catenin was reduced, a nd the cytoplasmic (P = 0.0050) and nuclear (P = 0.0001) expressions increa sed from ACF to adenoma to carcinoma. These data suggest that ACF and their aberrant expression of beta -catenin play a role in colon tumorigenesis.