Although the mutated p53 gene has been postulated to induce immunohistochemically-detectable p53
protein, reports regarding the relationship between p53 mutation and p53
protein expression have been contradictory. This study investigated the relationship between p53 mutations and p53 expression and their clinical significance for patients with
transitional cell carcinoma of the bladder. Eighty-seven
transitional cell carcinoma of the bladder were analyzed by immunohistochemistry (IHC) for p53 nuclear accumulation, and the results compared to mutations detected in the p53 gene evaluated by polymerase chain reaction single-strand conformation polymorphism (SSCP) and DNA sequence analysis. By p53 IHC analysis, positive p53 staining was observed in 50 (57.5%) of the 87
tumors. The specificity of IHC, defined as a percentage of IHC negative (<20%)
tumors among
tumors without mutation, was 94.6%. Despite the good concordance between p53 mutation and p53
protein expression (p<0.0001), 48.0% (24/50) of the
tumors showed p53 overexpression without mutation, and 2 (5.4%)
tumors with mutation showed no p53 immunoreactivity. Patients with higher grade (grade 3), stage (stages pT2-4), and p53 mutations had a poorer prognosis by Kaplan-Meier survival analysis. A Cox univariate analysis found that grading (hazard ratio 3.139; p=0.002), staging (hazard ratio 3.832; p=0.0005) and p53 mutation (hazard ratio 2.498; p=0.013) were significant variables in these patients, but no variable was independently associated with an increased survival of bladder
carcinoma by multivariate analysis. We found that a 20% cut-off level of p53 overexpression showed the highest correlation with prognosis and p53 mutation, however, p53 overexpression and mutation were not superior to staging as prognostic markers. These data suggest that careful assessment of the TNM staging system remains the most reliable predictive
indicator of survival for patients with
transitional cell carcinoma of the bladder.