Does polysomy of chromosome 17 have a role in ERBB2 and topoisomerase IIα expression?: Gene, mRNA and protein expression: A comprehensive analysis

Objectives: ERBB2 is an oncogene with prognostic and predictive value. Topoisomerase IIα is an enzyme encoding close to the ERBB2 oncogene, that represents a molecular target for anthracyclines. An indirect mechanism of increasing ERBB2 and topoisomerase IIα gene copy number is chromosome 17 polysomy. The aim of the present study was to clarify the implication of polysomy 17 in ERBB2 and topoisomerase IIα expression. In addition, we assessed the relation of ERBB2 and topoisomerase IIα gene dosage to mRNA and protein levels. Methods: We selected 83 cases diagnosed as invasive breast cancer. We analysed ERBB2 and topoisomerase IIα genes, mRNA and protein by fluorescence in situ hybridisation, real-time reverse-transcription polymerase chain reaction and immunohistochemistry. Results: We observed a progressive increase in mRNA expression from 0+ to 3+ and also a significant difference in the ERBB2 RNA levels between normal and amplified cases. We found that polysomy of chromosome 17 does not affect the ERBB2 expression and that topoisomerase IIα mRNA expression is not related to gene status. Conclusions: Our results demonstrate that polysomy of chromosome 17 is not related to ERBB2 expression. Thereby, it is important to use centromeric probes to clearly discriminate between true ERBB2 gene amplification and polysomy of chromosome 17. Copyright © 2007 S. Karger AG.