title: Prognostic and predictive implications of EGFR mutations, EGFR copy number and KRAS mutations in advanced stage lung adenocarcinoma.
abstract: OBJECTIVE
  Gefitinib and erlotinib were shown to be particularly effective in a clinically selected subpopulation of non-small cell lung cancer patients (NSCLC): adenocarcinoma histology, non-smoking status, Asian origin and female gender have been associated with improved clinical benefit compared to the unselected NSCLC population. The aim of the present study was to investigate the prognostic and predictive role of EGFR and KRAS analysis in advanced lung adenocarcinomas, selected according to clinical features associated to better response to EGFR tyrosine kinase inhibitors (TKIs), namely female gender and non-smoker or former light smoker status.
  
  
  METHODS
  EGFR and KRAS mutations and EGFR FISH status were assessed in 67 surgical samples.
  
  
  RESULTS
  EGFR and KRAS mutations were found in 16 (26.7%) and 12 (17.9%) patients, respectively. FISH analysis was positive in 34 (56.7%) patients. EGFR-mutated patients showed significantly longer survival when treated with EGFR TKIs (p = 0.002, hazard ratio (HR) = 0.036, 95% confidence interval (CI): 0.004 -0.303). KRAS mutations was found to be an independent negative prognostic factor in multivariate analysis (p = 0.008, HR = 3.52, 95% CI: 1.39-8.9). The prognostic value of EGFR FISH status was not confirmed in multivariate analysis (p = 0.048, HR = 0.47, 95%CI: 0.22-0.99).
  
  
  CONCLUSIONS
  In a group of clinically selected patients, EGFR and KRAS analysis was able to define distinct molecular subsets of lung adenocarcinoma.
authors.affiliation: Department of Medical Oncology 2, Istituto Oncologico Veneto-IRCCS, 64, I-35128 Padua, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonanno
authors.forename: Marco
authors.initials: M
authors.lastname: Schiavon
authors.forename: Giorgia
authors.initials: G
authors.lastname: Nardo
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertorelle
authors.forename: Laura
authors.initials: L
authors.lastname: Bonaldi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galligioni
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Giulia
authors.initials: G
authors.lastname: Pasello
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
authors.forename: Adolfo
authors.initials: A
authors.lastname: Favaretto
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018628:Gene Dosage; D018773:Genes, erbB-1; D011905:Genes, ras; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies