Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy

Cancer Sci. 2007 Sep;98(9):1336-43. doi: 10.1111/j.1349-7006.2007.00557.x. Epub 2007 Jul 19.

Abstract

Expression of excision repair cross-complementation group 1 (ERCC1), p53, or thioredoxin (TRX) is reported to be correlated with resistance to platinum-based drugs. The authors evaluated whether ERCC1, p53, or TRX expression could predict progression-free and/or overall survival in relapsed non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Immunohistochemistry was used to examine the expression of these three proteins in resected lung tumor samples obtained from 67 patients treated with platinum-based chemotherapy against recurrent tumors after curative resection. Immunostaining for ERCC1, p53, and TRX was positive in 29, 35, and 24 patients, respectively. Patients negative for ERCC1 had a significantly longer median progression-free (44 vs 26 weeks, P = 0.0075) and overall (73 vs 44 weeks, P = 0.0006) survival than those positive for ERCC1. Patients negative for p53 expression had a significantly longer median overall (70 vs 62 weeks, P = 0.0289), but not progression-free (37.5 vs 36 weeks, P = 0.2465), survival than those positive for p53 expression. From multivariate analysis, negative ERCC1 expression (hazard ratio [HR] = 1.3740, P = 0.0147) was a significantly favorable factor for progression-free survival, and negative ERCC1 expression (HR = 1.6533, P = 0.0018) and better performance status (HR = 1.9117, P = 0.0017) were significantly favorable factors for overall survival. This retrospective study indicates that immunostaining for ERCC1 may be useful for predicting survival in NSCLC patients receiving platinum-based chemotherapy against recurrent tumors after curative resection and can provide critical information for planning personalized chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • DNA Repair*
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Disease-Free Survival
  • Endonucleases / analysis*
  • Endonucleases / biosynthesis
  • Endonucleases / genetics
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Platinum Compounds / therapeutic use*
  • Predictive Value of Tests
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Platinum Compounds
  • Tumor Suppressor Protein p53
  • VAC14 protein, human
  • ERCC1 protein, human
  • Endonucleases