Abstract
In humans, the ERBB2 gene amplification and overexpression are biomarkers for invasive breast cancer and a therapeutic target. Also, TOP2α 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 ERBB2 and TOP2α status. In this study, and for the first time, the ERBB2 DNA status and RNA levels of intracellular (ICD) and extracellular (ECD) coding regions were compared with TOP2α gene status and expression profile, in samples of FMTs and disease-free tissues from the same animal. Results showed that ERBB2 and TOP2α 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 ERBB2 overexpression coupled with TOP2α overexpression (r=0.87, p<0.0001, n=27), being the ERBB2-ICD and ECD transcripts highly correlated (r=0.97, p<0.0001, n=27). Significant associations were found between TOP2α gene status or ERBB2 and TOP2α RNA levels with several clinicopathological parameters. This work highlights the need of experimental designs for a precise evaluation of ERBB2 and TOP2α 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.
Highlights
Feline mammary tumors (FMTs) are the third most common cancer in cat, usually highly malignant, infiltrative and metastatic [1, 2], representing a source of aggressive tumor types
De Maria and colleagues [15] reported that ERBB2 is overexpressed in mostly feline mammary lesions, suggesting that feline mammary tumors (FMTs) is a good model for ERBB2 overexpressing breast tumors with poor prognosis, Soares and co-authors [14] showed that ERBB2 is overexpressed in about 33% of FMTs indicating that is a suitable model to study ERBB2 positive breast cancers without gene amplification
Knowing that ERBB2 and TOP2α genes are located in the same chromosome in human and cat genomes, we analyzed the DNA copy number of ERBB2 (Figure 1a, Supplementary Table 1) and TOP2α genes (Figure 1b, Supplementary Table 2) in a collection of feline mammary tumors (n=27), always in comparison with the disease-free tissue from the same individual
Summary
Feline mammary tumors (FMTs) are the third most common cancer in cat, usually highly malignant, infiltrative and metastatic [1, 2], representing a source of aggressive tumor types. ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2, known as HER2) is one of the most studied oncogenes, being considered a breast cancer biomarker (at the gene www.aging-us.com and protein levels), commonly overexpressed in HBC [6]. Studies regarding the intracellular and extracellular domains showed that frequently ERBB2 can be present in truncated forms, being these works highly relevant to predict therapeutic-resistances to ERBB2-targeted drugs (e.g., monoclonal antibodies and small tyrosine kinase inhibitors) [8]. De Maria and colleagues [15] reported that ERBB2 is overexpressed in mostly feline mammary lesions, suggesting that FMT is a good model for ERBB2 overexpressing breast tumors with poor prognosis, Soares and co-authors [14] showed that ERBB2 is overexpressed in about 33% of FMTs indicating that is a suitable model to study ERBB2 positive breast cancers without gene amplification. Since the above-mentioned studies used different technical approaches and evaluated different tumor samples, further research is needed to clarify the role of the ERBB2 status in the oncogenesis of FMTs towards the validation of new molecular assays and ERBB2targeted therapies in cat
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
