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

The aberrant expression of β-catenin in colon tumors and the discovery of β-catenin mutations in small adenomas suggest that alterations of β-catenin are early events in human colorectal carcinogenesis. Here, we describe the expression of β-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 β-catenin expression by immunohistochemistry. Normal colonic epithelial cells adjacent to these lesions showed strong membranous expression of β-catenin and lacked cytoplasmic and nuclear expression. Cytoplasmic expression of β-catenin was seen in 25 of 46 ACF with dysplasia and in 2 of 48 ACF with atypia. In ACF with dysplasia, reduced membranous expression of β-catenin was associated with increased nuclear (P = 0.0013) and cytoplasmic (P = 0.0247) expression. The membranous (P = 0.0003) expression of β-catenin was reduced, and the cytoplasmic (P = 0.0016) and nuclear (P = 0.0266) expressions increased in ACF according to their degree of dysplasia. Likewise, membranous (P = 0.0007) expression of β-catenin was reduced, and the cytoplasmic (P = 0.0050) and nuclear (P = 0.0001) expressions increased from ACF to adenoma to carcinoma. These data suggest that ACF and their aberrant expression of β-catenin play a role in colon tumorigenesis.