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

ABSTRACT

OBJECTIVES: The expression of p21(WAF-1/CIP-1), a downstream regulator of p53, is a universal cycline-dependent kinase inhibitor. The aim of this study is to determine whether p21 expression could be used as a prognostic marker 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 results with the status of nuclear p53 and mdm2 accumulation, expression of type IV collagen in the basement membranes and upregulation of metalloproteinases (MMP-1, MMP-2, MMP-9). RESULTS: p21(WAF-1/CIP-1) immunoreactivity was observed in 51.7% of the tumors, and in only 39% of the tumors with functional p53 loss (nuclear accumulation of p53 and/or mdm2). p21(WAF-1/CIP-1) overexpression was not associated with grade and stage of the tumors and presence or absence of concomitant CIS. Moreover, p21(WAF-1/CIP-1) overexpression was not associated with upregulation of metalloproteinases or destruction of type IV collagen of basement membranes. CONCLUSIONS: Our results suggest that p21(WAF-1/CIP-1) expression is regulated by both p53-dependent and independent pathways and is not related to grade, stage or potential markers of invasion in urothelial carcinomas.