title: Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib.
abstract: BACKGROUND
  Biological markers for optimal selection of patient to epidermal growth factor receptor (EGFR)-targeted therapies are not established in advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  EGFR/HER2 gene copy number by FISH, EGFR protein and pAKT expression by immunohistochemistry (IHC) and EGFR and KRAS mutations were tested in 204 gefitinib-treated NSCLC patients.
  
  
  RESULTS
  Increased EGFR and HER2 gene copy number (FISH+), EGFR protein overexpression (IHC+), EGFR mutations and pAKT overexpression were all associated with significantly higher response rates (33%, 29%, 22%, 39% and 20% respectively). EGFR FISH+ (32%) and IHC+ (61%) correlated with improved survival, while EGFR mutations (27%), KRAS mutations (26%) and pAKT expression (69%) did not. In multivariate survival analysis EGFR FISH and IHC were independent predictive markers. EGFR FISH+/IHC+ patients (23%) had a median survival of 21 months versus 6 months for double-negative patients (30%).
  
  
  CONCLUSIONS
  Combination of EGFR FISH and IHC is effective predictor for benefit from gefitinib. Patients with double-negative results are unlikely to benefit in western NSCLC populations.
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Health Sciences Center and Cancer Center, Aurora, CO 80010, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: M
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: F
authors.initials: F
authors.lastname: Cappuzzo
authors.forename: J
authors.initials: J
authors.lastname: McCoy
authors.forename: L
authors.initials: L
authors.lastname: Bemis
authors.forename: A C
authors.initials: AC
authors.lastname: Xavier
authors.forename: R
authors.initials: R
authors.lastname: Dziadziuszko
authors.forename: P
authors.initials: P
authors.lastname: Gumerlock
authors.forename: K
authors.initials: K
authors.lastname: Chansky
authors.forename: H
authors.initials: H
authors.lastname: West
authors.forename: A F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: L
authors.initials: L
authors.lastname: Crino
authors.forename: D R
authors.initials: DR
authors.lastname: Gandara
authors.forename: W A
authors.initials: WA
authors.lastname: Franklin
authors.forename: P A
authors.initials: PA
authors.lastname: Bunn
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018628:Gene Dosage; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib