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Advances in Brief |
Departments of Pathology [X. P. H., T. G. P., T. P. P.] and Epidemiology and Biostatistics [J. S. R.], Case Western Reserve University School of Medicine and Cancer Center, Cleveland, Ohio 44106
The aberrant expression of ß-catenin in colon tumors and the discovery of ß-catenin mutations in small adenomas suggest that alterations of ß-catenin are early events in human colorectal carcinogenesis. Here, we describe the expression of ß-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 ß-catenin expression by immunohistochemistry. Normal colonic epithelial cells adjacent to these lesions showed strong membranous expression of ß-catenin and lacked cytoplasmic and nuclear expression. Cytoplasmic expression of ß-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 ß-catenin was associated with increased nuclear (P = 0.0013) and cytoplasmic (P = 0.0247) expression. The membranous (P = 0.0003) expression of ß-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 ß-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 ß-catenin play a role in colon tumorigenesis.
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