The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection

Lung Cancer. 2010 Jun;68(3):478-83. doi: 10.1016/j.lungcan.2009.07.004. Epub 2009 Aug 15.

Abstract

Objectives: The DNA repair pathway and isotype composition of beta-tubulin are known to be associated with resistance to platinum- and taxane-based chemotherapy, respectively. The aim of this study was to identify the clinical significance of excision repair cross-complementation 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), X-ray repair cross-complementation 1 (XRCC1) and betaIII-tubulin on the chemotherapy response and overall survival in patients with non-small cell lung cancer (NSCLC) who received neoadjuvant chemotherapy.

Methods: Protein expression profiles were evaluated by immunohistochemistry on surgical specimens of 82 NSCLC patients who underwent platinum- and taxane-based neoadjuvant chemotherapy. The expression levels of proteins were measured semi-quantitatively and the correlation with tumor responses, pathologic cell death rate and survival were evaluated.

Results: There were 73 (89.0%) clinical stage III patients. Lobectomy, bilobectomy, and pneumonectomy were performed in 54 (65.0%), 11 (13.4%), and 17 (20.7%) patients, respectively. There was no correlation between clinical response and protein expression. The expression levels of ERCC1, BRCA1, and XRCC1 increased proportionally to the cell death rate (p<0.05); however, betaIII-tubulin expression did not correlate with cell viability. Multivariate analysis demonstrated that early pathologic stage, adjuvant chemotherapy, high ERCC1 and low betaIII-tubulin expression were good prognostic factors for overall survival (p<0.05).

Conclusions: The inverse correlation between DNA repair proteins and cell viability suggests that these protein expression levels can be markers for chemotherapy responsiveness. However, only ERCC1 and betaIII-tubulin were prognostic factors after platinum- and taxane-based neoadjuvant chemotherapy following surgical resection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / metabolism
  • Bridged-Ring Compounds / administration & dosage
  • Bridged-Ring Compounds / adverse effects
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Neoplasm
  • Endonucleases / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • Platinum Compounds / administration & dosage
  • Platinum Compounds / adverse effects
  • Pneumonectomy*
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Tubulin / metabolism
  • X-ray Repair Cross Complementing Protein 1

Substances

  • BRCA1 Protein
  • Bridged-Ring Compounds
  • DNA-Binding Proteins
  • Platinum Compounds
  • TUBB3 protein, human
  • Taxoids
  • Tubulin
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • taxane
  • ERCC1 protein, human
  • Endonucleases