title: EGFR R497K polymorphism is a favorable prognostic factor for advanced lung cancer.
abstract: BACKGROUND
  It has been reported that the R497K polymorphism of the epidermal growth factor receptor (EGFR) gene has attenuated functions in ligand binding, tyrosine kinase activation, and growth stimulation. On other hand, EGFR gene mutations at kinase domain in non-small cell lung cancer (NSCLC) have been examined for their ability to predict sensitivity to gefitinib or erlotinib.
  
  
  METHODS
  We investigated the EGFR mutations and/or R497K polymorphism statuses in 225 surgically treated NSCLC cases. 192 adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of exon 13 was analyzed by PCR-RFLP method.
  
  
  RESULTS
  EGFR mutations at kinase domain were found from 95 of 225 lung cancer patients. In 86.2% of patients, homo- or heterozygous Lys497 allele was present. No correlation existed between R497K EGFR genotype and clinico-pathological features, such as gender, smoking status, and pathological subtypes.
  
  
  CONCLUSIONS
  EGFR mutation status was not correlated with R497KEGFR genotype of lung cancers. In node-negative patients, R497KEGFR genotype was not correlated with disease outcome. In node-positive patients, however, R497K EGFR was significantly associated with better overall survival. This association was attributable to neo-adjuvant or adjuvant chemotherapy. In 46 total gefitinib treated NSCLC patients, the prognosis was not different between the EGFR wild type (GG) patients and AG+AA patients. R497KEGFR polymorphism might be associated with favorable prognosis of advanced lung cancers and correlated with chemosensitivity.
authors: Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. hisasaki@med.nagoya-cu.ac.jp
authors: Hidefumi
authors: H
authors: Sasaki
authors: Katsuhiro
authors: K
authors: Okuda
authors: Shigeki
authors: S
authors: Shimizu
authors: Minoru
authors: M
authors: Takada
authors: Masaaki
authors: M
authors: Kawahara
authors: Naoto
authors: N
authors: Kitahara
authors: Meinoshin
authors: M
authors: Okumura
authors: Akihide
authors: A
authors: Matsumura
authors: Keiji
authors: K
authors: Iuchi
authors: Tomoya
authors: T
authors: Kawaguchi
authors: Akihito
authors: A
authors: Kubo
authors: Osamu
authors: O
authors: Kawano
authors: Haruhiro
authors: H
authors: Yukiue
authors: Motoki
authors: M
authors: Yano
authors: Yoshitaka
authors: Y
authors: Fujii
mesh_terms: D019943:Amino Acid Substitution; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000601:surgery*; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000601:surgery*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D004273:DNA, Neoplasm; D066246:ErbB Receptors