The impact of epidermal growth factor receptor gene status on gefitinib-treated Japanese patients with non-small-cell lung cancer

Shuji Ichihara, Shinichi Toyooka, Yoshiro Fujiwara, Katsuyuki Hotta, Hisayuki Shigematsu, Masaki Tokumo, Junichi Soh, Hiroaki Asano, Kouichi Ichimura, Keisuke Aoe, Motoi Aoe, Katsuyuki Kiura, Kenji Shimizu, Hiroshi Date, Nobuyoshi Shimizu

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105 Citations (Scopus)

Abstract

We investigated the relationships between genetic factors and clinical outcome in Japanese non-small-cell lung cancer (NSCLC) patients treated with gefitinib. Ninety-eight NSCLC patients who had been treated with gefitinib, were screened for mutations in epidermal growth factor receptor (EGFR) exons 18-21, KRAS exon2, and polymorphisms including the CA simple sequence repeat in intronl (CA-SSR1) and single nucleotide polymorphisms in the promoter region (-216G/T and -191C/A), using a PCR-based assay and direct sequencing. The EGFR copy number status was also evaluated using a fluorescence in situ hybridization assay. EGFR and KRAS mutations were found in 38 (38.8%) and 8 (8.2%) of the 98 patients, respectively. A high EGFR copy number status was identified in 31 (41.3%) of the 75 assessable patients. Drug-sensitive EGFR mutations limited to exon19 deletions and L858R were independent predictive factors of a stronger sensitivity to gefitinib (p = 0.0002), the overall survival (OS) (p = 0.0036), and prolonged progression-free survival (PFS) (p < 0.0001). The EGFR copy number status was not related to a sensitivity to gefitinib and prolonged OS and PFS. Regarding polymorphisms, patients with a short CA-SSR1 showed a prolonged OS as compared with those with a long length in patients with a drug-sensitive EGFR mutation, although this difference was not significant (p = 0.13). Thus, drug-sensitive EGFR mutations predict a favorable clinical outcome and a high EGFR copy number may not be related to clinical benefits in gefitinib-treated Japanese patients with NSCLC. Our findings also suggest that the CA-SSR1 length may influence the clinical outcome in patients with a drug-sensitive EGFR mutation.

Original languageEnglish
Pages (from-to)1239-1247
Number of pages9
JournalInternational Journal of Cancer
Volume120
Issue number6
DOIs
Publication statusPublished - Mar 15 2007

Keywords

  • Amplification
  • EGFR
  • Gefitinib
  • Mutation
  • NSCLC
  • Polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Ichihara, S., Toyooka, S., Fujiwara, Y., Hotta, K., Shigematsu, H., Tokumo, M., Soh, J., Asano, H., Ichimura, K., Aoe, K., Aoe, M., Kiura, K., Shimizu, K., Date, H., & Shimizu, N. (2007). The impact of epidermal growth factor receptor gene status on gefitinib-treated Japanese patients with non-small-cell lung cancer. International Journal of Cancer, 120(6), 1239-1247. https://doi.org/10.1002/ijc.22513