p21(WAF-1/CIP-1), a downstream regulator of functional p53 loss, in transitional cell carcinoma of urothelium

Objectives: The expression of p21(WAF-1/CIP-1), a downstream regulator of p 53, is a universal cycline-dependent kinase inhibitor. The aim of this stud y is to determine whether p21 expression could be used as a prognostic mark er in urothelial carcinomas. Methods: By use of immunohistochemistry, we examined the expression of p21( WAF-1/CIP-1) in 60 patients with urothelial carcinomas and compared the res ults with the status of nuclear p53 and mdm2 accumulation, expression of ty pe IV collagen in the basement membranes and upregulation of metalloprotein ases (MMP-1, MMP-2, MMP-9). Results: p21(WAF-1/CIP-1) immunoreactivity was observed in 51.7% of the tum ors, and in only 39% of the tumors with functional p53 loss (nuclear accumu lation of p53 and/or mdm2). p21(WAF-1/CIP-1) overexpression was not associa ted with grade and stage of the tumors and presence or absence of concomita nt CIS, Moreover, p21(WAF-1/CIP-1) overexpression was not associated with u pregulation of metalloproteinases or destruction of type IV collagen of bas ement membranes. Conclusions: Our results suggest that p21(WAF-1/CIP-1) expression is regula ted by both p53-dependent and independent pathways and is not related to gr ade, stage or potential markers of invasion in urothelial carcinomas. Copyr ight (C) 2000 S. Karger AG. Basel.