Predictive value of microtubule associated proteins tau and stathmin in patients with nonmuscle invasive bladder cancer receiving adjuvant intravesical taxane therapy

J Urol. 2011 Nov;186(5):2094-100. doi: 10.1016/j.juro.2011.06.051. Epub 2011 Sep 23.

Abstract

Purpose: After encouraging results from 2 clinical trials performed at our institution to test intravesical taxane based chemotherapy for bacillus Calmette-Guérin refractory, nonmuscle invasive bladder cancer we designed a study to identify molecular markers linked to the optimal response to such treatment modality.

Materials and methods: Included in the institutional review board approved study were 32 patients with nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer who received intravesical taxane chemotherapy, that is docetaxel or nanoparticle albumin-bound paclitaxel. Immunophenotype analysis on tissue samples obtained before intravesical taxane therapy was done using a panel of molecular markers, including Ki-67, p53, and the microtubule associated proteins tau and stathmin.

Results: Increased total tau (cytoplasmic and nuclear) and stathmin expression before intravesical taxane therapy was significantly associated with decreased recurrence-free survival (p <0.0001 and 0.007, respectively). A tau positive phenotype was an independent prognostic factor for recurrence-free survival on multivariate analysis (HR 15.66, 95% CI 2.68-91.71, p = 0.002). Neither the proliferation index assessed by Ki-67 expression nor p53 status was significantly associated with recurrence-free survival.

Conclusions: Assessment of tau and stathmin protein expression should be considered to select patients before intravesical taxane based chemotherapy for nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer since those who have tumors with low tau/stathmin protein expression show a better response to therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intravesical
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • BCG Vaccine / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Bridged-Ring Compounds / administration & dosage*
  • Bridged-Ring Compounds / therapeutic use
  • Carcinoma, Transitional Cell / drug therapy
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / mortality*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / genetics
  • Male
  • Microtubules
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Stathmin / metabolism*
  • Taxoids / administration & dosage*
  • Taxoids / therapeutic use
  • Treatment Failure
  • Tumor Suppressor Protein p53 / genetics
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / mortality*
  • tau Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • BCG Vaccine
  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • Ki-67 Antigen
  • Stathmin
  • Taxoids
  • Tumor Suppressor Protein p53
  • tau Proteins
  • taxane