CD44 Expression in Colorectal Adenomas Is an Early Event Occurring Prior to K-ras and p53 Gene Mutation

Abstract

Neoplastic progression of colorectal epithelial cells from benign adenomas to malignant carcinomas appears to result from a series of genetic alterations involving both oncogenes and tumor suppressor genes. This progression was recently found to be associated with expression of splice variant isoforms of CD44, a cell surface hyaluronate receptor implicated in carcinogenesis. In this study we examined the relationship of CD44 expression to somatic genetic events in the adenoma-carcinoma sequence: point mutation of K-ras in codons 12 and 13 and overexpression of p53 protein as a marker of gene mutation. Among 22 small adenomas, CD44 was present in 9 (41%), of which only 1 contained a K-ras mutation. CD44 was absent in the other 2 small adenomas positive for K-ras mutation or p53 overexpression. In contrast to the early expression of CD44 in small adenomas, mutations of K-ras and p53 were detected preferentially in large adenomas and late-stage adenomas containing carcinoma. The frequent expression of CD44 prior to K-ras and p53 gene alterations in colorectal neoplasia suggests that activation of CD44 gene expression is related to earlier events in the adenoma-carcinoma sequence, possibly cell activation and proliferation following APC gene mutation or alteration of DNA methylation.