Annals of Oncology Advance Access originally published online on December 16, 2008
Annals of Oncology 2009 20(4):696-702; doi:10.1093/annonc/mdn679
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lung cancer |
Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer
1 Department of Internal Medicine, National Taiwan University Hospital, Taipei
2 Division of Critical Care Medicine, Department of Emergency and Critical Care Medicine, Lotung Poh-Ai Hospital, Yi-Lan
3 Department of Pathology, National Taiwan University Hospital, Taipei
4 Department of Molecular Biotechnology, Da-Yeh University, Chang-Hua
5 Department of Oncology, National Taiwan University Hospital, Taipei
6 Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
* Correspondence to: Dr J.-Y. Shih, M.D., Ph.D., Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan. Tel: +886-2-23123456 ext 62905; Fax: +886-2-2358-2867; E-mail: jyshih{at}ntu.edu.tw
Background: Mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) treatment. A recent study has suggested that 33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by immunohistochemistry analysis. We intended to find out whether the EGFR mutations of primary lung cancers are concordant to that of corresponding metastatic tumors.
Materials and methods: We analyzed EGFR exons 18–21 from paired primary and metastatic tumors in 67 lung cancer patients who had not received TKI before tissues were sampled.
Results: Using the direct sequencing method, 9 of 18 (50%) patients with EGFR mutation-positive primary lung tumors had lost the mutations in metastases. For 26 patients who were EGFR mutation positive in the metastatic tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases).
Conclusion: EGFR mutations in primary lung tumors do not always reflect the same situation in metastases. Analysis of EGFR mutations in the primary lung tumor would be inadequate for planning the use of TKI for advanced NSCLC.
Key words: EGFR, metastasis, mutation, non-small-cell lung cancer
Received for publication November 4, 2007. Revision received September 20, 2008. Accepted for publication September 24, 2008.