Expression of p21(waf1/cip1) Protein in Transitional Cell Bladder Tumours and Its Prognostic Value

Abstract

Objectives: p21(waf1/cip1) protein is a cyclin-dependent kinase inhibitor able to arrest the cell at the G₁ phase by inhibiting DNA replication through interaction with proliferating cell nuclear antigen (PCNA). Experimental analyses of human bladder cancer cell lines show that p21 might be considered a tumour suppressor gene since it is able to induce apoptosis like p53. The prognostic value and expression of p21(waf1/cip1) is incompletely studied in bladder cancer at present. Methods: The expression of p21 protein was immunohistochemically analysed in paraffin-embedded specimens of 186 patients with primary transitional cell bladder tumours. The results of immunohistochemical analysis were related to known prognostic factors and complete long clinical follow-up data (over 11 years). Results: The expression of p21(waf1/cip1) protein was significantly related to DNA ploidy, S phase fraction, mitotic index, apoptotic index, morphometric nuclear factors, and the expression of p53 and PCNA proteins, whereas it was unrelated to grade or TNM classification. In univariate survival analysis, the expression of p21(waf1/cip1) protein was not significantly related to prognosis. Independent prognostic factors were T category, papillary status and mitotic index. Conclusion: The results indicate that although the expression of p21(waf1/cip1) protein is related to indicators of cell proliferation, apoptosis and p53 expression, it has no better prognostic value than already established prognostic factors in bladder cancer.