Evangelos Tsiambas1,2, Nicholas S Mastronikolis3, Alicia Y Lefas4, Stavros N Georgiannos5, Vasileios Ragos6, Panagiotis P Fotiades7, Nikolaos Tsoukalas8, Nikolaos Kavantzas2, Andreas Karameris9, Dimitrios Peschos10, Efstratios Patsouris2, Konstantinos Syrigos11. 1. Department of IHC & Molecular Biology, 401 GAH, Athens, Greece tsiambasecyto@yahoo.gr. 2. Department of Pathology, Medical School, University of Athens, Athens, Greece. 3. Department of ENT, Head and Neck Surgery, Medical School, University of Patras, Patras, Greece. 4. Faculty of Medicine, University of Southampton, Southampton, U.K. 5. Department of Breast Surgery, Blue Cross Hospital Breast Cancer Action Fund, London, U.K. 6. Department of Maxillofacial, School of Medicine, University of Ioannina, Ioannina, Greece. 7. Department of Surgery, Leicester General Hospital, Leicester, U.K. 8. Department of Oncology, 417 VA Hospital (NIMTS), Athens, Greece. 9. Department of Pathology, 417 VA Hospital (NIMTS), Athens, Greece. 10. Department of Physiology, Medical School, University of Ioannina, Ioannina, Greece. 11. 3rd Department of Medicine, Athens School of Medicine, "Sotiria" General Hospital, Athens, Greece.
Abstract
BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) over-activation is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Our aim was to investigate the role of chromosome 7 multiplication with regard to its influence in EGFR expression, combined or not with gene amplification. MATERIALS AND METHODS: Using tissue microarray technology, fifty (n=50) primary NSCLCs were cored and re-embedded into the final recipient block. Immunohistochemistry (IHC) and also chromogenic in situ hybridization (CISH) were performed. RESULTS: EGFR expression at any level was detected in 40/50 (80%) cores. Over-expression was observed in 23/40 (57.5%) cases. Gene amplification was identified in 11/50 (22%) cases whereas chromosome 7 polysomy in 8/50 (16%) cases. Pure chromosome 7 multiplication alone led to low or moderate levels of expression. Overall EGFR expression was correlated with gene (p=0.001) and interestingly with chromosome 7 centromere numerical imbalances (p=0.004). CONCLUSION: EGFR expression is associated not only with amplification, but also with chromosome 7 centromere multiple copies. Chromosome 7 multiplication -due to centromere region amplification or true polysomy- is critical for applying monoclonal antibody targeted therapeutic strategies excluding the pure non-amplified cases. Copyright
BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) over-activation is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Our aim was to investigate the role of chromosome 7 multiplication with regard to its influence in EGFR expression, combined or not with gene amplification. MATERIALS AND METHODS: Using tissue microarray technology, fifty (n=50) primary NSCLCs were cored and re-embedded into the final recipient block. Immunohistochemistry (IHC) and also chromogenic in situ hybridization (CISH) were performed. RESULTS:EGFR expression at any level was detected in 40/50 (80%) cores. Over-expression was observed in 23/40 (57.5%) cases. Gene amplification was identified in 11/50 (22%) cases whereas chromosome 7 polysomy in 8/50 (16%) cases. Pure chromosome 7 multiplication alone led to low or moderate levels of expression. Overall EGFR expression was correlated with gene (p=0.001) and interestingly with chromosome 7 centromere numerical imbalances (p=0.004). CONCLUSION:EGFR expression is associated not only with amplification, but also with chromosome 7 centromere multiple copies. Chromosome 7 multiplication -due to centromere region amplification or true polysomy- is critical for applying monoclonal antibody targeted therapeutic strategies excluding the pure non-amplified cases. Copyright
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