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Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer

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Abstract

To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR amplification and EGFR protein expression statuses in 27 surgically treated non-small-cell lung cancer (NSCLC) cases. These patients experienced relapse after surgery and received gefitinib 250 mg/day. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR mutations were found from 15/27 lung cancer patients. EGFR mutation status was significantly correlated with better prognosis (log-rank test = 0.0023). Smoking status (never smoker vs. smoker, = 0.0032), and pathological subtypes (adenocarcinoma vs. non-adenocarcinoma, = 0.0011), but not EGFR amplification (= 0.1278), were correlated with survival of lung cancers. EGFR IHC results were correlated with FISH results (= 0.0125), but not correlated with prognosis (= 0.7921). Thus, the EGFR gene amplification or protein expression is not a predictor of gefitinib efficacy in Japanese patients with NSCLC. We have also evaluated the EGFR mutation status and clinico-pathological features for 27 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. The EGFR mutation status, especially exon19 mutation was correlated with good response to gefitinib than exon 21 point mutation.

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Acknowledgments

We thank Nihon Gene Research Laboratories Inc. (Drs. Narusawa and Shimada) for suggesting that they use fluorescence in situ hybridization to test for epidermal growth factor receptor gene amplification. Grant Sponsor: 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)

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Correspondence to Hidefumi Sasaki.

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Sasaki, H., Endo, K., Okuda, K. et al. Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer. J Cancer Res Clin Oncol 134, 569–577 (2008). https://doi.org/10.1007/s00432-007-0320-z

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  • DOI: https://doi.org/10.1007/s00432-007-0320-z

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