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

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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.

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Acknowledgments

The authors would like to thank Mrs. Emi Sugiyama for his excellent technical assistances. This work was supported by AstraZeneca Research Grant 2004, Grand-in-Aid for Research in Nagoya City University (2006), and Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science (JSPS) (Nos, 19390367, 18390381,18659407).

Conflict of interest statement

None declared.

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Authors and Affiliations

  1. Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Hidefumi Sasaki, Katsuhiro Okuda, Osamu Kawano, Haruhiro Yukiue, Motoki Yano & Yoshitaka Fujii

  2. Department of Pathology II, Nagoya City University Medical School, Nagoya, Japan

    Shigeki Shimizu

  3. Department of Internal Medicine, National Hospital Organization, Kinki-chuo Chest Medical Center, Sakai, Osaka, Japan

    Minoru Takada, Masaaki Kawahara, Tomoya Kawaguchi & Akihito Kubo

  4. Department of Surgery, National Hospital Organization, Kinki-chuo Chest Medical Center, Sakai, Osaka, Japan

    Naoto Kitahara, Meinoshin Okumura, Akihide Matsumura & Keiji Iuchi

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  1. Hidefumi Sasaki
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  2. Katsuhiro Okuda
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  3. Shigeki Shimizu
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  10. Tomoya Kawaguchi
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  13. Haruhiro Yukiue
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  14. Motoki Yano
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  15. Yoshitaka Fujii
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Correspondence to Hidefumi Sasaki.

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Sasaki, H., Okuda, K., Shimizu, S. et al. EGFR R497K polymorphism is a favorable prognostic factor for advanced lung cancer. J Cancer Res Clin Oncol 135, 313–318 (2009). https://doi.org/10.1007/s00432-008-0464-5

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  • DOI: https://doi.org/10.1007/s00432-008-0464-5

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