title: Activating mutations within the EGFR kinase domain: a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma.
abstract: OBJECTIVE
  Although epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations are highly predictive of response to EGFR TK inhibitors in advanced non-small-cell lung cancer (NSCLC), a prognostic value of EGFR mutations in resected NSCLC has not been established.
  
  
  METHODS
  We retrospectively reviewed 117 patients with primary lung adenocarcinoma who underwent surgical resection between 1995 and 2005. Nucleotide sequencing of the kinase domain of EGFR (exons 18-21) was performed using nested PCR amplification of individual exons.
  
  
  RESULTS
  Forty-eight patients (41.8%) harbored exon 19 deletion or exon 21 point mutations. EGFR mutations were more frequently found in never-smoker (P = 0.04) or in smaller-sized primary tumor (P = 0.001). A presence of EGFR mutations was significantly associated with longer disease-free survival (DFS) (20.1 vs. 34.4 months in mutated EGFR; P = 0.003). In multivariate analysis of DFS, wild-type EGFR was associated with a higher risk of recurrence, with an adjusted hazard ratio of 1.42 (95% CI, 1.1-2.41, P = 0.04), as compared to mutated EGFR. However, no significant association was observed between EGFR mutations and overall survival (P = 0.39). Isolated brain metastasis as the first recurrence after resection was found more frequently in those patients with tumors bearing EGFR mutations, although the difference was not statistically significant (9 vs. 24% in mutated EGFR, P = 0.15).
  
  
  CONCLUSIONS
  Activating mutations within the EGFR TK domain can be used to predict the risk of recurrence in curatively resected pulmonary adenocarcinoma.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, CPO Box 8044, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Park
authors.forename: Moo-Suk
authors.initials: MS
authors.lastname: Park
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
authors.forename: Kyung Young
authors.initials: KY
authors.lastname: Chung
authors.forename: Se Kyu
authors.initials: SK
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Chang
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Moon
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D017434:Protein Structure, Tertiary / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D010770:Phosphotransferases