Prognostic significance of survivin, β-catenin and p53 expression in urothelial carcinoma.

Abstract

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p <0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p <0.01; r=0.236, p <0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies.