title: Comprehensive analysis of epidermal growth factor receptor gene status in lung adenocarcinoma.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) gene status including tyrosine kinase domain somatic mutations, increased copy number, and protein overexpression are reported to be associated with response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer. The purpose of this study was to elucidate the prevalence of activated EGFR gene and the association between mutation, copy number, and protein overexpression.
  
  
  METHODS
  In a cohort of consecutive patients with lung adenocarcinoma, polymerase chain reaction and direct sequencing (n = 89) were conducted through exons 18 to 21. Fluorescence in situ hybridization (FISH) (n = 89) and single-nucleotide polymorphism (SNP) array 6.0 (n = 77) were used to detect the gene copy number. The protein expression of EGFR was detected by standard immunohistochemistry (IHC) (n = 89).
  
  
  RESULTS
  Fifty-nine (66.3%) patients harbored somatic mutations of EGFR in tyrosine kinase domain, 55.1% were positive by IHC and 44.9% were positive by FISH, and 66.2% showed gain of copy number according to SNP array 6.0. EGFR somatic mutations are more common in women, never smokers, and tumors with better differentiation. Increased copy number detected by both FISH and SNP array 6.0 analysis is significantly correlated with mutations of EGFR.
  
  
  CONCLUSIONS
  The EGFR somatic mutation rate is significantly higher in Chinese patients with lung adenocarcinoma than western countries. Nevertheless, we found comparable FISH and IHC-positive rates between different ethnics. Considering that FISH may be affected by tumor heterogeneity and other factors, SNP array 6.0 analysis is a good alternative method to detect EGFR copy number variations.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Li
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Fang
authors.forename: Xiangkun
authors.initials: X
authors.lastname: Han
authors.forename: Rong
authors.initials: R
authors.lastname: Fang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D002681:China; D015331:Cohort Studies; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D066246:ErbB Receptors