EXPRESSION OF MUTANT P53 PROTEIN AND CD44 VARIANT PROTEINS IN COLORECTAL TUMORIGENESIS

Colorectal tumorigenesis evolves through a series of molecular genetic changes, providing putative markers for tumour progression. This study investigated the relation between expression of the tumour suppressor gene p53 and splice variants v5 and v6 of the cell adhesion molecule CD44 by immunohistochemistry on tissue samples of early adenomas (n=12), late adenomas (n=12), Dukes's A and B carcinomas (n=21), and Dukes's C and D carcinomas (n=22) and compared these results with expression of these proteins in normal colonic mucosa (n=17). A statistically significant trend of increasing expression was seen for both p53 (p<0.005) and CD44 variant exon v6 (p<0.0005) in subsequent stages of this tumour progression model. High expression of CD44 v5 was seen in most colorectal neoplasms (83%-96%), independent of stage. A statistically significant correlation was present between p53 expression and expression of variant v6 of CD44 (p<0.01). Both p53 expression and CD44 v6 expression in adenomas increased with the degree of dysplasia (p<0.05). The results of this study show that mutant p53 protein and variant v6 of the CD44 glycoprotein are markers of tumour progression in colorectal cancer.