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Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas
An immunohistochemical and fluorescence in situ hybridization study
Article first published online: 14 FEB 2005
Copyright © 2005 American Cancer Society
Volume 103, Issue 6, pages 1265–1273, 15 March 2005
How to Cite
Suzuki, S., Dobashi, Y., Sakurai, H., Nishikawa, K., Hanawa, M. and Ooi, A. (2005), Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas. Cancer, 103: 1265–1273. doi: 10.1002/cncr.20909
- Issue published online: 2 MAR 2005
- Article first published online: 14 FEB 2005
- Manuscript Accepted: 24 NOV 2004
- Manuscript Revised: 19 NOV 2004
- Manuscript Received: 1 SEP 2004
- nonsmall cell lung carcinomas;
- epidermal growth factor receptor;
- fluorescence in situ hybridization;
Recently, molecular therapies targeting epidermal growth factor receptor (EGFR) have been developed for clinical use. The current study was conducted to determine 1) the exact frequency of EGFR protein overexpression, 2) the correlation between protein overexpression and EGFR amplification, and 3) the correlation between the status of the genetic and clinicopathologic features in nonsmall cell lung carcinomas (NSCLC).
In total, 181 NSCLC samples were examined immunohistochemically using an antibody against EGFR, and tumor cells that exhibited overexpression were examined further for EGFR amplification by fluorescence in situ hybridization.
Overexpression of EGFR protein was found in 34% of the tumors. Among these, EGFR amplification was demonstrated in 74%. High-level gene amplification was found exclusively in tumors cells with high protein expression. In most of these tumors, cells that exhibited EGFR overexpression and gene amplification were distributed heterogeneously, even within a single tumor nodule. Statistically, EGFR overexpression was correlated significantly with lymph node metastasis and with a more advanced pathologic stage. Moreover, in adenocarcinomas, gene amplification was correlated significantly with lymph node metastasis and tended to be correlated with a more advanced pathologic stage.
The overexpression of EGFR in NSCLC was accompanied predominantly, but not exclusively, by gene amplification. It is important to evaluate not only protein overexpression but also the EGFR status to design adjuvant therapies for patients with NSCLC, because specimens that exhibit both protein overexpression and gene amplification may predict eventual lymph node metastasis and, possibly, aggressive tumor behavior. Cancer 2005. © 2005 American Cancer Society.