title: Predictive value of microtubule associated proteins tau and stathmin in patients with nonmuscle invasive bladder cancer receiving adjuvant intravesical taxane therapy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, Columbia University College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Wosnitzer
authors.forename: Josep
authors.initials: J
authors.lastname: Domingo-Domenech
authors.forename: Mireia
authors.initials: M
authors.lastname: Castillo-Martin
authors.forename: Chad
authors.initials: C
authors.lastname: Ritch
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mansukhani
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylack
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
authors.forename: James M
authors.initials: JM
authors.lastname: McKiernan
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001500:BCG Vaccine / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000235:genetics; D008297:Male; D008870:Microtubules; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D050777:Stathmin / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D019394:Ki-67 Antigen; D050777:Stathmin; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D016875:tau Proteins; C080625:taxane