Expression of survivin and its spliced variants in bladder tumors as a potential prognostic marker

Abstract

Introduction: Survivin, a novel inhibitor of apoptosis, is re-expressed in a vast majority of human cancers and is widely considered as a diagnostic marker of cancers. Survivin protein regulates both cell division and apoptosis. There are at least 5 spliced variants of the gene with different subcellular localization and anti-apoptotic property. We examined the expression pattern of survivin and its 2 spliced variants, survivin-deltaEx3 and survivin-2B, and their prognostic values in archival collections of formalin-fixed paraffin-embedded samples of bladder tumors.

Materials and methods: Total RNA from formalin-fixed paraffin-embedded samples (51 samples from 30 patients with bladder cancer and 5-year follow-up) were extracted and analyzed by semiquantitative reverse transcriptase polymerase chain reaction technique. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry.

Results: The expression of survivin, survivin-deltaEx3, and survivin-2B were detected in 66.6%, 47.8%, and 54.7% of the specimens, respectively. The expression of survivin and survivin-deltaEx3 were preferentially elevated in tumors with higher grades, whereas survivin-2B expression was lower in high-grade tumors (P = .04). A reverse correlation was observed between survivin-2B expression and high-grade tumors. Immunohistochemistry results also confirmed the nuclear localization of survivin protein within tumoral cells.

Conclusion: We were successful in detecting the expression of survivin and its variants in formalin-fixed paraffin-embedded bladder samples. Furthermore, our results showed that overexpression of survivin and survivin-deltaEx3 in bladder tumors correlates with poor prognosis of bladder cancer. We suggest that survivin and its variants are suitable prognostic markers of bladder tumors.