Expression of p21(WAF1/CIP1) in colorectal adenomas and adenocarcinomas and its correlation with p53 protein expression

The expression of p53-inducible cyclin-dependent kinase inhibitor, p21(WAF1/CIP1) in non-neoplastic mucosa, adenoma and adenocarcinoma of the colorectum was examined by immunohistochemistry and western blotting and its relation with the expression of p53 protein was analyzed. Nonneoplastic epithelial cells at the surface area showing no proliferative activity expressed p21(WAF1/CIP1). The expression of p21(WAF1/CIP1) immunohistochemically detected in 55% (206/377) of the adenomas and 66% (190/289) of the adenocarcinomas, respectively. The incidence of strongly positive cases was significantly higher in the adenocarcinomas (27%) than in the adenomas (18%) (P<0.05). The incidence of cases with strong p21(WAF1/CIP1) expression was higher in stages 0, 1 and 2 carcinomas than in stages 3 and 4 carcinomas (P<0.05). A decrease in the incidence of cases with strong expression was detected in carcinomas invading deeper than muscularis propria. The incidence of strongly positive cases was significantly lower in carcinomas with lymph node metastasis than those without metastasis (P<0.05). The expression of p21 as well as p53 detected by western blotting was compatible with the results of immunohistochemistry in most cases examined. However, there was no significant correlation between the expression of p21(WAF1/CIP1) and the abnormal accumulation of p53. These findings overall suggest that: (i) the physiological expression of p21(WAF1/CIP1) may be associated with cellular senescence of colorectal mucosa; (ii) reduced expression of p21(WAF1/CIP1) may participate in the progression of colorectal carcinoma; and (iii) p53-independent pathway may be considerably involved in the induction of p21(WAF1/CIP1).