CD44 splice variants as prognostic markers in colorectal cancer.

Splice variants of CD44 play a causal role in the metastatic spread of pancreatic carcinoma in the rat. In previous studies we have shown that homologues of these CD44 isoforms (CD44v6) are overexpressed during colorectal tumorigenesis in man and that CD44v6 overexpression is associated with an unfavorable prognosis in this disease. In the present study we have assessed the prognostic significance of CD44 variants containing exon v5. In addition, we have used a panel of different antibodies against CD44v6 and applied a combined scoring system to improve its value as prognosticator. Expression of CD44 variants was studied by immunohistochemistry on frozen tissue sections, and the prognostic value of the CD44 variant expression was assessed using univariate and multivariate analysis. Our studies show that expression of CD44v6, but not CD44v5, has significant prognostic value. Analysis of CD44v6 expression by means of a combined scoring system, on the basis of a panel of three different monoclonal antibodies (mAbs), makes CD44v6 a highly significant prognostic marker that is independent of Dukes stage, tumor grade, or tumor localization. Assessment of CD44v6 expression by a combination of mAbs yields an independent prognosticator that may be of value in identifying patients with a high propensity to develop distant metastasis.