Expression of ERCC1 and class III beta-tubulin in non-small cell lung cancer patients treated with a combination of cisplatin/docetaxel and concurrent thoracic irradiation

Cancer Chemother Pharmacol. 2009 Aug;64(3):565-73. doi: 10.1007/s00280-008-0907-3. Epub 2009 Jan 3.

Abstract

Introduction: The expression of excision repair cross-complementation group 1 (ERCC1) is reported to be correlated with resistance to platinum-based drugs. Class III beta-tubulin is reported to be correlated with resistance to taxanes.

Methods: In the present study, we evaluated whether ERCC1 and class III beta-tubulin expression could be used to predict progression-free and/or overall survival in 34 patients with locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemoradiation therapy with cisplatin and docetaxel, and immunohistochemistry was used to examine the expression of these two proteins in tumor samples obtained from the patients.

Results: Immunostaining for ERCC1 and class III beta-tubulin was positive in 16 and 12 patients, respectively. A significant correlation was observed between ERCC1 expression and response to chemotherapy (P = 0.012), and between class III beta-tubulin expression and histology (P = 0.029). Patients negative for ERCC1 had a significantly longer median progression-free (62.5 vs. 36 weeks, P = 0.009), but not overall (171 vs. 50.5 weeks, P = 0.208), survival than those positive for ERCC1. Expression of class III beta-tubulin was not correlated with progression-free or overall survival (P = 0.563 and P = 0.265, respectively). Multivariate analysis adjusting for possible confounding factors showed that negative ERCC1 expression (hazard ratio = 3.972, P = 0.009) was a significantly favorable factor for progression-free survival.

Conclusions: This retrospective study indicates that immunostaining for ERCC1 may be useful for predicting survival in NSCLC patients receiving concurrent chemoradiotherapy with cisplatin and docetaxel, and can provide information critical for planning personalized chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Endonucleases / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Rate
  • Taxoids / administration & dosage
  • Tubulin / genetics*

Substances

  • DNA-Binding Proteins
  • TUBB3 protein, human
  • Taxoids
  • Tubulin
  • Docetaxel
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin