p21(WAF1/CIP1) expression in colorectal carcinomas: its correlation with p53 mutations and p53 and Ki67 immunohistochemistry.

Mutations of the p53 gene are the most common genetic alteration in maligna nt human tumors. A cyclin-dependent kinase inhibitor, p21(WAF1/CIP1), thoug ht to be an important mediator of p53-induced cell cycle arrest. Although n umerous studies have reported p53 expression and mutation in colorectal can cer few of them have correlated p53 expression with that of its downstream effector p21 and with the proliferation index as measured by expression of the Ki67 nuclear antigen. We studied p53, p21 and Ki67 expression by immuno histochemistry and molecular biology in 35 colorectal carcinomas. We compar ed these findings with each other and with clinical factors. Sixty three pe rcent of tumors expressed p53 whereas seventy one percent expressed p21(WAF 1/CIP1). In adenocarcinomas, p21 staining was heterogeneous: p21-reactive c ells were seen in the most differentiated areas. There was no correlation b etween p21(WAF1/CIP1) and p53 expression, p53 mutation, Ki67 expression or clinical factors such as sex or location of the tumer. On the other hand,th ere was a statistical relationship between p21 expression and survival: our results indicated an association between high p21 expression and lower sta ges p21(WAF1/CIP1) appears to be induced independently of p53 in these tumo rs and may be associated with differentiation rather than proliferation. (C ) 2001 Editions scientifiques et medicales Elsevier SAS.