title: Prognostic value of EGFR mutations in surgically resected pathological stage I lung adenocarcinoma.
abstract: OBJECTIVE
  With the advent of the molecular-targeted therapy, rapid progress has been made in the treatment of advanced or recurrent non-small-cell lung cancer (NSCLC). Although surgical complete resection remains the standard and most promising treatment, the clinical significance of epidermal growth factor receptor (EGFR) gene mutations in early-stage NSCLC remains uncertain.
  
  
  METHODS
  We investigated the prognostic value of EGFR mutations in surgically resected pathological stage I NSCLC. A total of 388 consecutive patients with NSCLC who underwent complete tumor resection in our hospital from 2006 through 2008 were studied retrospectively. Formalin-fixed, paraffin-embedded tissue sections were used to isolate DNA from carcinoma lesions. Mutational analyses of EGFR gene were performed by loop-hybrid mobility shift assay, a highly sensitive polymerase chain reaction-based method.
  
  
  RESULTS
  Mutations of EGFR were detected in 185 of the 388 patients (47.7%). EGFR mutations were more frequently found in women (110 of 185, 59.5%), adenocarcinoma (183 of 185, 98.9%), patients with no vascular invasion (139 of 185, 75.1%) and nonsmokers (106 of 185, 57.3%). In patients with pathological stage I adenocarcinoma, both overall survival (OS) and disease-free survival (DFS) were significantly higher in patients with EGFR mutation than in those with wild-type EGFR. Furthermore, patients with exon 21 mutation have better DFS than those with exon 19 mutation in stage IB adenocarcinoma. Cox's proportional hazard model indicated that EGFR status was an independent variable for predicting the OS and DFS in patients with pathological stage IB adenocarcinoma.
  
  
  CONCLUSIONS
  Our results suggest that EGFR mutations might be a prognostic factor in patients with pathological stage I lung adenocarcinoma.
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.|Pathology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Nishii
authors.affiliation: Pathology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
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 Medical Oncology and Cancer Center, Shiga University of Medical Science Hospital, Otsu, Japan.
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Isaka
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Furumoto
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Saito
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Oshita
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Kouzo
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Matsukuma
authors.affiliation: Departments of Thoracic Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000601:surgery*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: adenocarcinoma; epidermal growth factor receptor; non-small-cell lung cancer; pathological stage I; prognostic factor