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Research Paper|Volume 11, Issue 13|pp 4688—4705

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

Daniela Ferreira1,2, Maria Soares3, Jorge Correia4, Filomena Adega1,2, Fernando Ferreira4, Raquel Chaves1,2
  • 1CAG - Laboratory of Cytogenomics and Animal Genomics, Department of Genetics and Biotechnology, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
  • 2BioISI - Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Lisbon 1749-016, Portugal
  • 3Research Center for Biosciences and Health Technologies (CBiOS), Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias (ULHT), Lisbon 1749-024, Portugal
  • 4CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, Lisbon 1300-477, Portugal
* Equal contribution
Received: March 8, 2019Accepted: July 2, 2019Published: July 12, 2019

Copyright: Ferreira et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.