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

Urol J. 2009 Spring;6(2):101-8.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery
  • Cohort Studies
  • Cystectomy / methods
  • Cystectomy / mortality
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA Splicing
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Survival Analysis
  • Survivin
  • Tissue Culture Techniques
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Survivin