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

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BACKGROUND: Increase of EGFR gene copy number consequent to gene amplification and/or polysomy of chromosome 7 has been significantly associated with better clinical outcome in Non Small Cell Lung Cancer (NSCLC) patients treated with Tyrosin-Kinase Inhibitors (TKIs).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.<br /><br />METHODS: 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.<br /><br />RESULTS: A discrepancy between FISH results obtained with UCCC scoring system and 7q31 control was evidenced in 2 patients (10%).<br /><br />CONCLUSION: 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.




Casorzo, L., Corigliano, M., Ferrero, P., Venesio, T., & Risio, M. (2009). Evaluation of 7q31 region improves the accuracy of EGFR FISH assay in non small cell lung cancer. Diagnostic Pathology, 4(1). https://doi.org/10.1186/1746-1596-4-36

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