Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma.

Abstract

To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer. We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan-Meier analysis and uni- and multivariate Cox regression analysis. Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46% had at least one pTa recurrence and 12% even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71% of patients with progression in contrast to only 40% in cases without progression (p=0.004). Of all progressed patients, 92% showed overexpression of survivin in their initial pTa specimen compared to 61% without progression (p=0.001). Kaplan-Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p=0.005) as well as overexpression of survivin (p=0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p=0.033) and multifocality (p=0.046) and tumor size over 3cm (p=0.042) were prognosticators for worse PFS. Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.