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

Matthew S. Wosnitzer, Josep Domingo-Domenech, Mireia Castillo-Martin, Chad Ritch, Mahesh Mansukhani, Daniel P. Petrylack, Mitchell C. Benson, James M. McKiernan, Carlos Cordon-Cardo

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 2.6891.71, 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.

Original languageEnglish (US)
Pages (from-to)2094-2100
Number of pages7
JournalJournal of Urology
Volume186
Issue number5
DOIs
StatePublished - Nov 2011
Externally publishedYes

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Stathmin
Microtubule-Associated Proteins
Urinary Bladder Neoplasms
Bacillus
tau Proteins
docetaxel
Recurrence
Drug Therapy
Survival
Therapeutics
Research Ethics Committees
Nanoparticles
Multivariate Analysis
taxane
Clinical Trials
Phenotype
Neoplasms

Keywords

  • BCG vaccine
  • carcinoma
  • stathmin
  • tau proteins
  • transitional cell
  • urinary bladder

ASJC Scopus subject areas

  • Urology

Cite this

Predictive value of microtubule associated proteins tau and stathmin in patients with nonmuscle invasive bladder cancer receiving adjuvant intravesical taxane therapy. / Wosnitzer, Matthew S.; Domingo-Domenech, Josep; Castillo-Martin, Mireia; Ritch, Chad; Mansukhani, Mahesh; Petrylack, Daniel P.; Benson, Mitchell C.; McKiernan, James M.; Cordon-Cardo, Carlos.

In: Journal of Urology, Vol. 186, No. 5, 11.2011, p. 2094-2100.

Research output: Contribution to journalArticle

Wosnitzer, MS, Domingo-Domenech, J, Castillo-Martin, M, Ritch, C, Mansukhani, M, Petrylack, DP, Benson, MC, McKiernan, JM & Cordon-Cardo, C 2011, 'Predictive value of microtubule associated proteins tau and stathmin in patients with nonmuscle invasive bladder cancer receiving adjuvant intravesical taxane therapy', Journal of Urology, vol. 186, no. 5, pp. 2094-2100. https://doi.org/10.1016/j.juro.2011.06.051
Wosnitzer, Matthew S. ; Domingo-Domenech, Josep ; Castillo-Martin, Mireia ; Ritch, Chad ; Mansukhani, Mahesh ; Petrylack, Daniel P. ; Benson, Mitchell C. ; McKiernan, James M. ; Cordon-Cardo, Carlos. / Predictive value of microtubule associated proteins tau and stathmin in patients with nonmuscle invasive bladder cancer receiving adjuvant intravesical taxane therapy. In: Journal of Urology. 2011 ; Vol. 186, No. 5. pp. 2094-2100.
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abstract = "Purpose: After encouraging results from 2 clinical trials performed at our institution to test intravesical taxane based chemotherapy for bacillus Calmette-Gu{\'e}rin 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-Gu{\'e}rin 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 2.6891.71, 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- Gu{\'e}rin refractory bladder cancer since those who have tumors with low tau/stathmin protein expression show a better response to therapy.",
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AU - Ritch, Chad

AU - Mansukhani, Mahesh

AU - Petrylack, Daniel P.

AU - Benson, Mitchell C.

AU - McKiernan, James M.

AU - Cordon-Cardo, Carlos

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N2 - 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 2.6891.71, 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.

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