title: Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR.
abstract: BACKGROUND
  Amplification of the fibroblast growth factor receptor 1 (FGFR1) gene has been described in tumors of non-small-cell lung cancer (NSCLC) patients. Prior reports showed conflicting rates of amplification frequency and clinical relevance.
  
  
  METHODS
  We developed a reliable real-time quantitative PCR assay to assess the frequency of FGFR1 amplification and assessed the optimal cutoff level of amplification for clinical application.
  
  
  RESULTS
  In a training cohort of 203 NSCLCs, we established that a 3.5-fold amplification optimally divided patients into groups with different survival rates with a clear threshold level. Those with FGFR1 amplification levels above 3.5-fold had an inferior survival. These data were confirmed in a validation cohort of 142 NSCLC. After adjusting for age, sex, performance status, stage, and histology, patients with FGFR1 amplification levels above 3.5 fold had a hazard ratio of 2.91 (95% CI- 1.14, 7.41; pvalue-0.025) for death in the validation cohort. The rates of FGFR1 amplification using the cutoff level of 3.5 were 5.1% in squamous cell and 4.1% in adenocarcinomas. There was a non-significant trend towards higher amplifications rates in heavy smokers (> 15 pack-years of cigarette consumption) as compared to light smokers.
  
  
  CONCLUSIONS
  Our data suggest that a 3.5-fold amplification of FGFR1 is of clinical importance in NSCLC. Our cutpoint analysis showed a clear threshold effect for the impact of FGFR1 amplification on patients' survival, which can be used as an initial guide for patient selection in trials assessing efficacy of novel FGFR inhibitors.
authors.affiliation: Karmanos Cancer Institute & Department of Oncology, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Shirish M
authors.initials: SM
authors.lastname: Gadgeel
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Michele L
authors.initials: ML
authors.lastname: Cote
authors.forename: Aliccia
authors.initials: A
authors.lastname: Bollig-Fischer
authors.forename: Susan
authors.initials: S
authors.lastname: Land
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005091:Exons; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*
chemical_list: D051496:Receptor, Fibroblast Growth Factor, Type 1