Immunohistochemical detection of p53 protein overexpression versus gene sequencing in urinary bladder carcinomas

Purpose: Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p 53 alterations in bladder tumors has not been established. The aim of the p resent study was to evaluate an immunohistochemical (IHC) method for the ro utine determination of p53 protein overexpression in human bladder tumors a nd to determine the relation between nuclear accumulation of p53 with the t raditional prognostic indicators and patient survival. Materials and Methods: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpres sion and direct DNA sequencing for p53 gene mutations. Results: The overexpression of p53 protein was reported in 30.8% of the cas es and mutations of p53 gene in 23.0%. A significant association was observ ed between p53 alterations established either by IHC or direct DNA sequenci ng and stage (p <0.0001), grade (p <0.001), vascular invasion (p =0.0005), DNA ploidy (p =0.0002) and carcinoma in situ (p <0.0001). The correlation b etween the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p <0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p <0.0001). However, in multivariate analysis, only stage was significantl y correlated to prognosis (p <0.0001). Conclusions: The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does n ot appear to have a better predictive prognostic value than stage in bladde r tumors.