Assessment of <i>ERBB2</i> and <i>TOP2α</i> gene status and expression profile in feline mammary tumors: findings and guidelines

Abstract

In humans, the <i>ERBB2</i> gene amplification and overexpression are biomarkers for invasive breast cancer and a therapeutic target. Also, <i>TOP2α</i> gene aberrations predict the response to anthracycline-based adjuvant chemotherapy. Although feline mammary tumors (FMTs) are good models in comparative oncology, scarce data is available regarding the <i>ERBB2</i> and <i>TOP2α</i> status. In this study, and for the first time, the <i>ERBB2</i> DNA status and RNA levels of intracellular (ICD) and extracellular (ECD) coding regions were compared with <i>TOP2α</i> gene status and expression profile, in samples of FMTs and disease-free tissues from the same animal. Results showed that <i>ERBB2</i> and <i>TOP2α</i> gene status are highly correlated (r=0.87, p<0.0001, n=25), with few tumor samples presenting amplification. Also, the majority of the FMTs showed <i>ERBB2</i> overexpression coupled with <i>TOP2α</i> overexpression (r=0.87, p<0.0001, n=27), being the <i>ERBB2</i>-ICD and ECD transcripts highly correlated (r=0.97, p<0.0001, n=27). Significant associations were found between <i>TOP2α</i> gene status or <i>ERBB2</i> and <i>TOP2α</i> RNA levels with several clinicopathological parameters. This work highlights the need of experimental designs for a precise evaluation of <i>ERBB2</i> and <i>TOP2α</i> gene status and its expression in FMTs, to improve their clinical management and to further validate them as a suitable model for comparative oncology studies.