title: DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.
abstract: BACKGROUND
  Adjuvant cisplatin-based chemotherapy improves survival among patients with completely resected non-small-cell lung cancer, but there is no validated clinical or biologic predictor of the benefit of chemotherapy.
  
  
  METHODS
  We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer. The patients had been enrolled in the International Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression. Overall survival was analyzed with a Cox model adjusted for clinical and pathological factors.
  
  
  RESULTS
  Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%). A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1 (test for interaction, P=0.009). Adjuvant chemotherapy, as compared with observation, significantly prolonged survival among patients with ERCC1-negative tumors (adjusted hazard ratio for death, 0.65; 95% confidence interval [CI], 0.50 to 0.86; P=0.002) but not among patients with ERCC1-positive tumors (adjusted hazard ratio for death, 1.14; 95% CI, 0.84 to 1.55; P=0.40). Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors (adjusted hazard ratio for death, 0.66; 95% CI, 0.49 to 0.90; P=0.009).
  
  
  CONCLUSIONS
  Patients with completely resected non-small-cell lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors do not.
authors.affiliation: Laboratory of Radiobiology and Oncology, Commissariat à l'Energie Atomique, Fontenay aux Roses, University of Paris 11, Paris, France.
authors.forename: Ken A
authors.initials: KA
authors.lastname: Olaussen
authors.forename: Ariane
authors.initials: A
authors.lastname: Dunant
authors.forename: Pierre
authors.initials: P
authors.lastname: Fouret
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brambilla
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Vincent
authors.initials: V
authors.lastname: Haddad
authors.forename: Estelle
authors.initials: E
authors.lastname: Taranchon
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
authors.forename: Helmut H
authors.initials: HH
authors.lastname: Popper
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.forename: Laure
authors.initials: L
authors.lastname: Sabatier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.forename: Thomas
authors.initials: T
authors.lastname: Tursz
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Chevalier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin