Class III beta-tubulin is a marker of paclitaxel resistance in carcinomas of unknown primary site

Cancer Chemother Pharmacol. 2007 Jun;60(1):27-34. doi: 10.1007/s00280-006-0343-1. Epub 2006 Sep 22.

Abstract

Purpose: In this study, we determine the prevalence and the prognostic value of the class III beta-tubulin microtubule protein examined immunohistochemically, in tumors of 40 patients with carcinomas of unknown primary site treated with paclitaxel-based chemotherapy.

Methods: Immunohistochemical intensity of staining and percentage of cells were quantified. Clinical characteristics, response to chemotherapy, progression-free survival, and overall survival were assessed for relationships with the expression of class III beta-tubulin.

Results: The response rate was 17.9% (seven partial responses among 39 valuable patients), while eleven patients had a stable disease (28.2%) and 21 patients progressed on therapy (53.8%). Patients with high class III beta-tubulin expression were more resistant to taxane-based chemotherapy, defined as progression under treatment, while patient characteristics were not found to be correlated with response to chemotherapy. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter overall survival, while there was a trend for an association with progression free survival. Multivariate analysis showed that class III beta-tubulin expression was independently correlated with progression free survival and overall survival.

Conclusions: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to paclitaxel and decreased survival in patients with carcinomas of unknown primary receiving paclitaxel-based chemotherapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers / analysis*
  • Carboplatin / administration & dosage
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Unknown Primary / drug therapy*
  • Neoplasms, Unknown Primary / metabolism
  • Neoplasms, Unknown Primary / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / therapeutic use*
  • Prognosis
  • Treatment Outcome
  • Tubulin / analysis*

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers
  • TUBB3 protein, human
  • Tubulin
  • Carboplatin
  • Paclitaxel