title: Mutations of the EGFR and K-ras genes in resected stage I lung adenocarcinoma and their clinical significance.
abstract: OBJECTIVE
  This study retrospectively assessed the mutations of the epidermal growth factor receptor (EGFR) and K-ras genes and their clinical significance in patients with resected stage I adenocarcinomas.
  
  
  METHODS
  A total of 354 patients with resected lung adenocarcinomas were included, and 256 patients with stage I disease were analyzed for the prognostic and predictive value of these mutations.
  
  
  RESULTS
  Mutations of EGFR and K-ras genes were detected in 149 (41.1 %) and 23 (6.4 %) of all tumors, and in 122 (47.6 %) and 14 (5.5 %) of stage I tumors, respectively. There were no significant differences in the disease-free survival (DFS) and overall survival (OS) between the EGFR-mutant and wild-type groups. However, the DFS and OS were significantly shorter in patients with K-ras mutations than in those without (5-year DFS: 50.8 vs. 76.9 %, 5-year OS: 70.0 vs. 86.6 %, p < 0.01). A multivariate analysis showed that K-ras mutations were an independent poor prognostic factor. Twenty-four of the 41 patients with recurrent disease after surgery were treated with an EGFR-TKI. Fifteen EGFR-mutant patients treated with an EGFR-TKI had a better prognosis than did the nine EGFR-wild-type patients.
  
  
  CONCLUSIONS
  The presence of an EGFR gene mutation was a predictive factor for the response to EGFR-TKI treatment in patients with resected stage I adenocarcinoma, but was not a prognostic factor. The presence of a K-ras gene mutation was a poor prognostic factor.
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan, taro.oba@gmail.com.
authors.forename: Taro
authors.initials: T
authors.lastname: Ohba
authors.forename: Gouji
authors.initials: G
authors.lastname: Toyokawa
authors.forename: Takuro
authors.initials: T
authors.lastname: Kometani
authors.forename: Kaname
authors.initials: K
authors.lastname: Nosaki
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hirai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Motoharu
authors.initials: M
authors.lastname: Hamatake
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugio
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases