Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression

Specific CD44 variant glycoproteins are overexpressed at particular stages of colorectal tumor progression. Some variants of the CD44 glycoprotein without exon v6 sequences appear at the earliest stage of tumorigenesis, i.e., in early adenomas. Expression of variants containing exon v6 sequences is largely restricted to the advanced stages of tumor development and in addition is more prevalent and intense in metastatic (Dukes C/D) than in nonmetastatic (Dukes A/B) carcinomas. The observation that CD44 variants containing a protein domain of CD44 that confers full metastatic potential to rat carcinoma and sarcoma cell lines is increasingly expressed during colorectal tumor progression indicates that this domain may have an important role in tumor progression and metastasis in humans. Information on v6 expression, which can be obtained by routine immunohistochemistry, may prove of important prognostic value, particularly in carcinomas (Dukes A and B) that have not yet given rise to detectable metastases.