Evaluation of 7q31 region improves the accuracy of EGFR FISH assay in non small cell lung cancer

The primary method to detect EGFR copy number is FISH (Fluorescence in Situ Hybridization), that in lung cancer requires a precise standardization due to the presence of intratumor heterogeneity and high frequency of chromosome 7 polysomy.Recommendations and interpretative guidelines to discriminate NSCLC patients into FISH positive (gene amplification and high chromosome 7 polysomy) and FISH negative have been proposed by the University of Colorado Cancer Center (UCCC). However, in a subset of cases the distinction between EGFR amplification and chromosome 7 polysomy can be controversial because of a complex pattern of multiple EGFR and centromere signals.In order to distinguish more accurately these two genetic events, 20 NSCLC FISH positive patients, showing a controversial pattern of EGFR and centromere specific signals, were further evaluated for the status of 7q31 distal region.A discrepancy between FISH results obtained with UCCC scoring system and 7q31 control was evidenced in 2 patients (10%).Our data strengthen the usefulness of 7q31 region evaluation to discriminate EGFR amplification from chromosome 7 polysomy in controversial EGFR FISH positive cases. Since it has been reported a possible different contribution of amplification and polysomy to TKIs susceptibility in NSCLC, the clear distinction between these two genetic events may be important to identify a subset of patients more responsive to the therapy.The development and clinical application of Tyrosine Kinase Inhibitors (TKIs) targeting the Epidermal Growth Factor Receptor (EGFR), such as erlotinib and gefitinib, provide important insights for the treatment of non small cell lung cancer (NSCLC). However, patients derive different degrees of benefit from treatment with EGFR TKIs [1-3]. Several molecular studies showed that sensitivity to EGFR TKIs correlated very strongly with a class of somatic activating mutations of EGFR kinase domain that target mainly two exons (19 and 21), indicating that pat