CD44V6 EXPRESSION IN HUMAN COLORECTAL-CARCINOMA

CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matr ix interactions. This transmembrane glycoprotein exists in either stan dard or variant forms, originated by alternative splicing. One of the isoforms (CD44V6) has been shown, in some systems, to modify the metas tatic potential of tumor cells. To investigate the role of this biomar ker as possible prognostic antigen in colorectal cancer, we immunohist ochemically anal)zed the distribution of CD44V6 expression on formalin -fixed, paraffin-embedded tissues from resected colorectal cancers of 34 patients. The monoclonal antibody VFF7 against the amino acid seque nce encoded by exon CD44V6 was applied using the avidin-biotin-peroxid ase method. For each resected specimen, normal (N), adenomatous (AD), and carcinomatous (CA) colonic mucosa were tested. In 68% of the resec ted cases, these areas were present in the same slide, and in 76% of c ases, nodal or liver metastases (MT) were available for evaluation. Ad enomatous polyp biopsy specimens of 10 carcinoma-free patients were al so tested. In selected cases, CD44V6 expression was also determined us ing the Western blot immunoprecipitation technique. CD44V6 immunoreact ivity was detected in 100% of the ADs, and in 91% of CAs, but was most ly weak in only 38% of MTs (n = 26). In 49% (n = 35) of ADs, 11% (n = 34) of CAs, and 4% of MTs (n = 26), the stain was moderate to strong. CD44V6 immunoreactivity was predominantly membranous in ADs and cytopl asmic in MTs. In the CAs, both staining patterns were noted. Interesti ngly, the normal mucosa had a weak subnuclear localization of the stai n. In the cases evaluated by Western blotting immunoprecipitation anal ysis, the level of CD44V6 protein expression was similar to that obtai ned by immunohistochemistry. No correlation was found with tumor type, stage, or patient survival. The predominant CD44VG expression in ADs and CAs, but not in MTs, suggests that, in many cases, the expression of this adhesion molecule may be lost during the acquisition of migrat ory function by the tumor cells. HUM PATHOL 29:627-635. Copyright (C) 1998 by W.B. Saunders Company.