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

• Published in: Journal of cancer research and clinical oncology 2009-02, Vol.135 (2), p.313-318
• Main Authors: Sasaki, Hidefumi, Okuda, Katsuhiro, Shimizu, Shigeki, Takada, Minoru, Kawahara, Masaaki, Kitahara, Naoto, Okumura, Meinoshin, Matsumura, Akihide, Iuchi, Keiji, Kawaguchi, Tomoya, Kubo, Akihito, Kawano, Osamu, Yukiue, Haruhiro, Yano, Motoki, Fujii, Yoshitaka
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Antineoplastic agents; Biological and medical sciences; Cancer Research; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - surgery; Chemotherapy; DNA, Neoplasm - genetics; Exons - genetics; Genes; Hematology; Humans; Internal Medicine; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - surgery; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Mutation; Oncology; Original Paper; Pharmacology. Drug treatments; Pneumology; Polymerase Chain Reaction; Polymorphism; Polymorphism, Genetic; Prognosis; Receptor, Epidermal Growth Factor - genetics; Tumors of the respiratory system and mediastinum
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-008-0464-5

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.