CD44 SPLICE VARIANTS AS PROGNOSTIC MARKERS IN COLORECTAL-CANCER

Background: Splice variants of CD44 play a causal role in the metastat ic spread of pancreatic carcinoma in the rat. In previous studies we h ave shown that homologues of these CD44 isoforms (CD44v6) are overexpr essed during colorectal tumorigenesis in man and that CD44v6 overexpre ssion 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 dif ferent antibodies against CD44v6 and applied a combined scoring system to improve its value as prognosticator. Methods: Expression of CD44 v ariants was studied by immunohistochemistry on frozen tissue sections, and the prognostic value of the CD44 variant expression was assessed using univariate and multivariate analysis. Results: Our studies show that expression of CD44v6, but not CD44v5, has significant prognostic value. Analysis of CD44v6 expression by means of a combined scoring sy stem, on the basis of a panel of three different monoclonal antibodies (mAbs), makes CD44v6 a highly significant prognostic marker that is i ndependent of Dukes stage, tumor grade, or tumor localization. Conclus ion: Assessment of CD44v6 expression by a combination of mAbs yields a n independent prognosticator that may be of value in identifying patie nts with a high propensity to develop distant metastasis.