A tissue microarray analysis on the role of chromosome 7 multiplication regarding the EGFR expression in non-small cell lung carcinomas

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Background: Epidermal growth factor receptor (EGFR) over activation is observed in significant proportions of NSCLC. Additionally, EGFR gene amplification is a significant genetic event leading to protein over expression in the majority of those cases. The role of chromosome 7 multiplication or true polysomy is still under investigation regarding its influence in EGFR expression. Methods: Using tissue microarray technology, fifty (n = 50) paraffin embedded, histologically confirmed primary NSCLCs were cored and re-embedded into a recipient block. Immunohistochemistry was performed for the determination of EGFR protein levels and chromogenic in situ hybridization (CISH) was also implemented (EGFR gene/CEP 7). Results: EGFR over expression (2+/3+) was observed in 23/40 (57.5%) cases correlated to the stage of the tumors (p = 0.001). EGFR gene amplification (low to high) was identified in 11/50 (22%) cases demonstrating a borderline association to its overall protein levels (p = 0.05), whereas chromosome 7 was detected in 8/50 (16%) cases. In three of them (n=3), gene amplification was also detected. Concerning the others (n=5), pure chromosome 7 multiplication alone led to a low or even moderate level of expression (2+,1+). Conclusions: EGFR expression levels are associated not only with gene amplification, but also to chromosome multiple signals. Chromosome 7 multiplication or true polysomy -after its clarification based not on FISH/CISH analysis but on comparative genomic hybridization (CGH) or similar molecular methods – is critical for handling those patients via monoclonal antibody targeted therapeutic strategies.

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