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 th e colorectum was examined by immunohistochemistry and western blotting and its relation with the expression of p53 protein was analyzed. Non neoplastic epithelial cells at the surface area showing no proliferati ve activity expressed p21(WAF1/CIP1). The expression of p21(WAF1/CIP1) immunohistochemically detected in 55% (206/377) of the adenomas and 6 6% (190/289) of the adenocarcinomas, respectively. The incidence of st rongly 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 carc inomas than in stages 3 and 4 carcinomas (P<0.05). A decrease in the i ncidence of cases with strong expression was detected in carcinomas in vading deeper than muscularis propria. The incidence of strongly posit ive cases was significantly lower in carcinomas with lymph node metast asis than those without metastasis (P<0.05). The expression of p21 as well as p53 detected by western blotting was compatible with the resul ts of immunohistochemistry in most cases examined. However, there was no significant correlation between the expression of p21(WAF1/CIP1) an d the abnormal accumulation of p53. These findings overall suggest tha t: (i) the physiological expression of p21(WAF1/CIP1) may be associate d with cellular senescence of colorectal mucosa; (ii) reduced expressi on of p21(WAF1/CIP1) may participate in the progression of colorectal carcinoma; and (iii) p53-independent pathway may be considerably invol ved in the induction of p21(WAF1/CIP1).