• Lorenzo Daniele, Paola Cassoni, Elisa Bacillo, Susanna Cappia, Luisella Righi, Marco Volante, Fabrizio Tondat, Giorgio Inghirami, Anna Sapino, Giorgio V Scagliotti, Mauro Papotti, and Silvia Novello.
• Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy. lorenzo.daniele@unito.it
• J Thorac Oncol. 2009 Jun 1; 4 (6): 684-8.

IntroductionThe majority of patients with non-small cell lung cancer (NSCLC) develop distant metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are capable of reducing brain and adrenal metastases. However, the EGFR status may be discordant between primary NSCLC and the corresponding metastases.MethodsUsing fluorescence in situ hybridization (FISH) analysis, the EGFR gene status was evaluated in a series of 38 cerebral or adrenal metastases collected from two institutions and in the corresponding primary tumors. Also, EGFR mutational analysis was performed using direct sequencing on the cerebral metastases.ResultsEGFR FISH was positive in 28% of the primary tumors and in 45% of the metastases (p < 0.05). Among the seven cases FISH-positive at the metastatic site but negative in the primary tumor, six were brain metastases, and one was an adrenal metastasis; all were polysomic for chromosome 7, none were amplified. No EGFR mutations have been found in the cerebral metastases.ConclusionBecause the molecular asset of EGFR may change during the metastatic progression of NSCLC to brain (but not to adrenal), the selection of patients with brain metastasis for specific targeted therapies by EGFR FISH analysis should be performed on metastatic lesions rather than on their corresponding primary tumors.

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