title: Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma.
abstract: OBJECTIVE
  The EGFR, K-ras, EML4-ALK, and BRAF genes are oncogenic drivers of lung adenocarcinoma. We conducted this study to analyze the mutations of these genes in stage I adenocarcinoma.
  
  
  METHODS
  The subjects of this retrospective study were 256 patients with resected stage I lung adenocarcinoma. We analyzed mutations of the EGFR, K-ras, and BRAF genes, and the EML4-ALK fusion gene. We also assessed disease-free survival (DFS) to evaluate the prognostic value and overall survival (OS) to evaluate the predictive value of treatment after recurrence.
  
  
  RESULTS
  Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes were detected in 120 (46.8 %), 14 (5.5 %), 6 (2.3 %), and 2 (0.8 %) of the 256 tumors. Two tumors had double mutations (0.8 %). The incidence of EGFR mutations was significantly higher in women than in men. The EML4-ALK fusion gene was detected only in younger patients. The DFS and OS of the K-ras mutant group were significantly worse than those of the EGFR mutant group, the EML4-ALK fusion gene group, and the wild-type group. Six of the seven patients with the EML4-ALK fusion gene are still alive without recurrent disease.
  
  
  CONCLUSIONS
  In patients with stage I adenocarcinoma, mutation of the K-ras gene was a poor prognostic factor for recurrence. The presence of a mutation of the EGFR or EML4-ALK gene was not a prognostic factor.
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ohba
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Gouji
authors.initials: G
authors.lastname: Toyokawa
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.|Department of Thoracic and Breast Surgery, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Osoegawa
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hirai
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Cancer Pathology Laboratory, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takenoyama
authors.affiliation: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan. ksugio@oita-u.ac.jp.|Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan. ksugio@oita-u.ac.jp.|Department of Thoracic and Breast Surgery, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan. ksugio@oita-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugio
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D018797:Cell Cycle Proteins / Q000235:genetics*; D066246:ErbB Receptors; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C415585:EML4 protein, human; D012697:Serine Endopeptidases
keywords: Adenocarcinoma; BRAF; EGFR; EGFR-TKI; EML4–ALK; K-ras; NSCLC