Significance of p57Kip2 Down-Regulation in Oncogenesis of Bladder Carcinoma: An Immunohistochemical Study

Abstract

Cyclin-dependent kinase inhibitors have important roles in the oncogenesis of various tumors including urothelial cancer. The aim of this study was to establish the importance of p57(Kip2), a unique cyclin-dependent kinase inhibitor, in the oncogenesis of bladder carcinoma. This article also focused on another cyclin-dependent kinase inhibitor, p27(Kip1), and telomerase enzyme and examined the relationship between these proteins. Thirty-one patients with urothelial carcinomas of the bladder and 7 cases with normal urinary bladder mucosa were included in the study. Immunohistochemical study was performed by monoclonal antibodies of p27(Kip1), p57(Kip2), and the telomerase subunit (hTERT). All immunohistochemical preparations were evaluated by an immunohistochemical histological score. p57(Kip2) and p27Kip1) expression were seen in all of the cases of normal mucosa. In carcinoma cases, 8 of 31 (25.8%) showed p57(Kip2) nuclear positivity and 20 of 31 (64.5%) expressed nuclear p27(Kip1). HSCOREs of carcinoma cases showed lower scores of nuclear p57(Kip2) and p27(Kip1) than normal mucosa, but only HSCOREs of nuclear p57(Kip2) (P = 0.001) showed statistical significance. Despite unknown significance, cytoplasmic p57(Kip2) and p27(Kip1) were also evaluated. Immunohistochemical analysis showed that carcinomas expressed higher HSCOREs of hTERT than normal mucosa, and there was a significant difference (P = 0.026) between muscle invasive carcinomas and normal mucosa. The data showed that p57(Kip2) down-regulation along with p27(Kip1) is a well-established feature of urothelial carcinoma. Probably, this down-regulation of cyclin-dependent kinase inhibitors supports the proliferation phase of oncogenesis. In the study, we also showed that hTERT expression was up-regulated in higher stages of urothelial carcinoma.