Predictive value of telomerase reverse transcriptase expression in patients with high risk superficial bladder cancer treated with adjuvant BCG immunotherapy

J Cancer Res Clin Oncol. 2009 Sep;135(9):1169-75. doi: 10.1007/s00432-009-0557-9. Epub 2009 Feb 12.

Abstract

Purpose: We conducted a prospective study to determine whether expression of telomerase reverse transcriptase (hTERT) is associated with recurrence-free-survival (RFS) or development of invasive disease in patients with high risk superficial bladder cancer (SBC) that received adjuvant BCG immunotherapy.

Methods: Thirty patients with high-grade T1 tumors were evaluated. Pre-BCG TURBT and post-BCG specimens were analyzed for hTERT nucleolar expression by immunohistochemistry.

Results: Post-BCG hTERT expression was statistically significantly lower than pre-BCG hTERT expression. Pre-BCG hTERT nucleolar staining in more than 75% of cells was associated with worse RFS (9 months vs. not yet reached, P = 0.05), while post-BCG hTERT nucleolar staining in more than 50% of the cells was associated with worse RFS (6 months vs. not yet reached, P = 0.001) and development of invasive disease. In multivariate analysis, post-BCG hTERT expression was independently associated with RFS and development of invasive disease.

Conclusions: Immunohistochemical evaluation of hTERT may help define a subset of high risk SBC patients that will eventually fail BCG and may therefore benefit from early salvage cystectomy.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Aged
  • Aged, 80 and over
  • BCG Vaccine / administration & dosage*
  • Disease-Free Survival
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Immunotherapy
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Telomerase / genetics*
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Adjuvants, Immunologic
  • BCG Vaccine
  • TERT protein, human
  • Telomerase