title: Epidermal Growth Factor Receptor Mutations and Prognosis in Pathologic N1-N2 Pulmonary Adenocarcinoma.
abstract: BACKGROUND
  Advanced unresectable pulmonary adenocarcinoma with the epidermal growth factor receptor (EGFR) exon 21 L858R point mutation (Ex21) is associated with a poor prognosis. However, for early-stage resectable adenocarcinoma, Ex21 tumors have a lower-grade malignancy than exon 19 deleted (Ex19) tumors. We therefore investigated the effect of EGFR mutations on the prognosis in patients with completely resected pN1-N2 adenocarcinoma.
  
  
  METHODS
  Five-year disease-free survival (DFS) and overall survival (OS) were analyzed in 202 pN1-N2 pulmonary adenocarcinoma patients, 100 of whom had EGFR mutations, comprising Ex21 in 41 (20.3%), Ex19 in 55 (27.2%), and Ex18 in 4 (2%).
  
  
  RESULTS
  Patients with and without EGFR mutations had similar DFS (26.2% vs 24.6%, respectively; p = 0.280) and OS (64.9% vs 54.2%, respectively; p = 0.564). Patients with Ex19 tumors had significantly better DFS (38.8% vs 11.8%, p = 0.001) and tended to have better OS (78.3% vs 48.3%, p = 0.123) than those with Ex21 tumors. For pN1, patients with Ex19 tumors had a longer disease-free interval (54.0 vs 22.3 months, p = 0.003) and median survival time (81.0 vs 50.6 months, p = 0.022) than those with Ex21 tumors. For pN2, patients with Ex19 tumors had longer disease-free interval than those with Ex21 tumors (43.6 vs 30.1 months, p = 0.109). Multivariate analysis showed Ex21 was a prognosticator of poor DFS (hazard ratio, 2.25; 95% confidence interval, 1.21 to 4.20).
  
  
  CONCLUSIONS
  For pN1-N2 pulmonary adenocarcinoma, Ex21 mutation was associated with poorer prognosis than Ex19 mutation. Thus, EGFR mutation status should be considered when predicting prognosis.
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan; Department of Surgery, Yokohama City University, Yokohama, Japan. Electronic address: 1401092k@yahoo.co.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Isaka
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nagata
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Furumoto
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Nishii
authors.affiliation: Cancer Prevention & Control Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Kouzo
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Surgery, Yokohama City University, Yokohama, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011013:Pneumonectomy; D011379:Prognosis
chemical_list: D066246:ErbB Receptors