title: Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma.
abstract: BACKGROUND
  Somatic mutations in EGFR (exons 19 and 21) and KRAS (exon 2) are found in lung adenocarcinomas and have potential prognostic value in patients with advanced disease. These mutations also have therapeutic significance, as they predict for sensitivity and resistance, respectively, to EGFR tyrosine kinase inhibitor therapy. Whether EGFR and KRAS mutations also have an impact on survival in patients who undergo lung resection for curative intent in the absence of targeted therapy has not been established.
  
  
  METHODS
  We analyzed the clinical characteristics and outcomes data for 296 patients who underwent resection at our institution for stage I-III lung adenocarcinoma. Tumors were assessed for both EGFR and KRAS mutations by established methods.
  
  
  RESULTS
  EGFR and KRAS mutations were found in tumors from 40 (14%) and 50 (17%) patients, respectively. Patients with EGFR mutant tumors were more likely to be never smokers (48%), present with stage I disease (88%), and had a 90% (95% confidence interval [CI] 70-97%) 3-year overall survival, whereas patients with KRAS mutant tumors were more likely to be former/current smokers (92%), present with locally advanced disease (40%), and had a 66% (95% CI 48-79%) 3-year overall survival.
  
  
  CONCLUSIONS
  EGFR and KRAS mutations define distinct molecular subsets of resected lung adenocarcinoma. Because EGFR and KRAS mutations also predict whether tumors are sensitive or resistant, respectively, to EGFR tyrosine kinase inhibitors, they can readily be used in clinical trials to help guide the administration of specific types of adjuvant therapy.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Jenifer L
authors.initials: JL
authors.lastname: Marks
authors.forename: Stephen
authors.initials: S
authors.lastname: Broderick
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Chitale
authors.forename: Allan R
authors.initials: AR
authors.lastname: Li
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Venkatraman E
authors.initials: VE
authors.lastname: Seshan
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: William
authors.initials: W
authors.lastname: Pao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016019:Survival Analysis
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors