Chromosome 7 Multiplication in EGFR-positive Lung Carcinomas Based on Tissue Microarray Analysis.

Abstract

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. 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. 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). 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.