Nuclear Expression of Mutant p53 protein in Transitinal Cell Carcinoma of the Bladder Detected by Immunohistochemistry: The Correlative Study with Proliferating Cell Nuclear Antigen Expression, Nucleolar Organizer Regions per Nucleus and Flow cytometric P

Cheon, Jun; Koh, Sung Kun

Abstract

We examined the nuclear overexpression of p53 protein by immunohistochemical analysis of the deparaffinized tumor tissue specimens from 45 patients with transitional cell carcinoma of the bladder. The data were then correlated with conventional prognostic variables such as histologic tumor grade, stage and DNA ploidy. In addition, we related the expression of the 53 protein to indicators of cellular proliferative activity, including proliferating cell nuclear antigen(PCNA), mean number of silver-binding nucleoar organizer regions(AgNORs) per nucleus, flow cytometric S-phase fraction(SPF) and proliferation index(PI). Survivals of the patients according to mutant p53 protein expression, stratified by histologic tumor grade and stage were analyzed.None of the urothelial cells from normal bladder specimens showed nuclear expression of mutant p53 protein. Mutant p53 protein expression was not associated with histologic tumor grade, stage, flow cytometric SPF and PI, but there was an association between mutant p53 protein expression and flow cytometric DNA ploidy with marginal statistical significance(p=0.0892) There was statistically significant difference of mutant p53 protein expression between low and high AgNORs counts per nucleus(p=0.0108), but here was no significant correlation between mutant p53 protein expression and PCNA expression rate. Using Kaplan-Meier analysis, we could not identify the statistically significant difference of survivorship between patients with and without mutant p53 expression. These results suggest that immunohistochemical analysis of bladder cancer specimens could be a good method of screening for the presence of mutant p53 protein, and mutant p53 protein expression may be an indicator of bladder cancer with more proliferative and/or aggressive activity, but it may not be an clinically useful prognostic factor in patients with bladder TCC.