title: Fibroblast growth factor receptor 1 gene amplification is associated with poor survival and cigarette smoking dosage in patients with resected squamous cell lung cancer.
abstract: OBJECTIVE
  To investigate the frequency and the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected squamous cell carcinoma of the lung (SCCL) and the association between smoking and FGFR1 amplification.
  
  
  METHODS
  Gene copy number of FGFR1 was investigated in microarrayed tumors from 262 patients with SCCL who had tumor tissue as well as smoking and survival data available. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1-amplified tumor (FGFR1 amp(+)) was prespecified as a tumor with nine or more copies of FGFR1.
  
  
  RESULTS
  Among 262 patients, the frequency of FGFR1 amp(+) was 13.0%. Patients with FGFR1 amp(+) had significantly shorter disease-free survival (DFS; 26.9 v 94.6 months; P < .001) as well as shorter overall survival (OS; 51.2 v 115.0 months; P = .002) than those without FGFR1 amp(+). Multivariate modeling confirmed that patients with FGFR1 amp(+) had a significantly greater risk of recurrence and death than those without FGFR1 amp(+) after adjusting for sex, smoking status, pathologic stage, and adjuvant chemotherapy (DFS: adjusted hazard ratio [AHR], 2.24; 95% CI, 1.45 to 3.45; P < .001; OS: AHR, 1.83; 95% CI, 1.15 to 2.89; P = .01). The frequency of FGFR1 amp(+) was significantly higher in current smokers than in former smokers and never-smokers (28.9% v 2.5% v 0%; P(trend) < .001). As the smoking dosage increased, so did the incidence of FGFR1 amp(+) (P(trend) = .002).
  
  
  CONCLUSIONS
  FGFR1 amplification is an independent negative prognostic factor in surgically resected SCCL and is associated with cigarette smoking in a dose-dependent manner. FGFR1 amplification is a relevant therapeutic target in Asian patients with SCCL.
authors.affiliation: Yonsei Cancer Center, Seoul, Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.forename: Dae Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Kang
authors.forename: Jin Gu
authors.initials: JG
authors.lastname: Lee
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Lim
authors.forename: Chang Young
authors.initials: CY
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Bae
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.forename: Ross Andrew
authors.initials: RA
authors.lastname: Soo
authors.forename: Kyung Young
authors.initials: KY
authors.lastname: Chung
authors.forename: Joo Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D012907:Smoking
chemical_list: D051496:Receptor, Fibroblast Growth Factor, Type 1