Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas - An immunohistomchemical and fluorescence in situ hybridization study

BACKGROUND. 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 carcinornas (NSCLC). METHODS. in total, 181 NSCLC samples were examined immunohistochemically using an antibody against FGFR, and tumor cells that exhibited overexpression were examined further for EGFR amplification by fluorescence in Situ hybridization. RESULTS. 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. fit 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. CONCLUSIONS. The overexpression of EGFR in NSCLC was accompanied preclominantly, 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 arnplification may predict eventual lymph node metastasis and, possibly, aggressive tumor behavior. Cancer 2005;103:1265-73. (C) 2005 American Cancer Society.