EGFR R497K polymorphism is a favorable prognostic factor for advanced lung cancer

  • Hidefumi Sasaki
  • Katsuhiro Okuda
  • Shigeki Shimizu
  • Minoru Takada
  • Masaaki Kawahara
  • Naoto Kitahara
  • Meinoshin Okumura
  • Akihide Matsumura
  • Keiji Iuchi
  • Tomoya Kawaguchi
  • Akihito Kubo
  • Osamu Kawano
  • Haruhiro Yukiue
  • Motoki Yano
  • Yoshitaka Fujii
Original Paper
  • 219 Downloads

Abstract

Introduction

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.

Materials and 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.

Keywords

EGFR Lung cancer Polymorphism R497K 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Hidefumi Sasaki
    • 1
  • Katsuhiro Okuda
    • 1
  • Shigeki Shimizu
    • 2
  • Minoru Takada
    • 3
  • Masaaki Kawahara
    • 3
  • Naoto Kitahara
    • 4
  • Meinoshin Okumura
    • 4
  • Akihide Matsumura
    • 4
  • Keiji Iuchi
    • 4
  • Tomoya Kawaguchi
    • 3
  • Akihito Kubo
    • 3
  • Osamu Kawano
    • 1
  • Haruhiro Yukiue
    • 1
  • Motoki Yano
    • 1
  • Yoshitaka Fujii
    • 1
  1. 1.Department of Surgery IINagoya City University Medical SchoolNagoyaJapan
  2. 2.Department of Pathology IINagoya City University Medical SchoolNagoyaJapan
  3. 3.Department of Internal MedicineNational Hospital Organization, Kinki-chuo Chest Medical CenterSakaiJapan
  4. 4.Department of SurgeryNational Hospital Organization, Kinki-chuo Chest Medical CenterSakaiJapan

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