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 p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. Materials and Methods: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. Results: The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing 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 between 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 significantly 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 not appear to have a better predictive prognostic value than stage in bladder tumors.