Expression of Multidrug Resistance ATP-Binding Cassette (ABC) Transporters in Canine Mammary Tumors
Breno S. Salgado1,2*, Suely Nonogaki3, Luisa M. Soares4, Angela Akamatsu5, Cristiano R. N. da Silva5, Thiago P. Anacleto5, Rodolfo Malagó5, Rafael M. Rocha3, Fátima Gärtner2, Noeme S. Rocha1,4
1Departamento de Patologia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Campus de Botucatu, Botucatu, Brazil.
2Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (Intitute of Biomedical Sciences Abel Salazar of University of Porto), Oporto, Portugal.
3Fundacao Antonio Prudente, Hospital A.C. Camargo, Sao Paulo, Brazil.
4Departamento de Clínica Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista, UNESP,. Botucatu, Brazil.
5Hospital Escola de Medicina Veterinária, Fundacao de Ensino e Pesquisa de Itajubá—FEPI, Itajubá, Brazil.
DOI: 10.4236/abcr.2015.43009   PDF    HTML     4,631 Downloads   5,426 Views   Citations


Mammary neoplasms are the most common tumors in female dogs. They are usually treated using solely surgical mastectomy—which is recognized as unsatisfactory in many cases. Given this, the benefits of chemotherapy in dogs with mammary cancer need to be further explored. Some drugs that can be used for treating canines with mammary tumors may be substrates of uptake and/or efflux transporters such as the ATP-binding cassette (ABC) transporters. Unfortunately, very little is known regarding the pathobiology of such proteins in canine tumors, including mammary cancer. Accordingly, this study was designed to characterize the expression of ABC transporters P-glycoprotein, MRP1, and MRP2 and their relation with clinicopathologic factors in order to allow a better understanding of their influence in canine mammary cancer. P-glycoprotein was expressed in tumors from 55.8% of patients, while MRP1 and MRP2 were expressed in 37.2% and 39.5% of tumors, respectively. P-glycoprotein expression showed to be related with regional lymph node spread (P = 0.0038), as well as with tumor grade (P = 0.0353) and with a shorter survival (P = 0.0245). MRP1 revealed a strong association with a higher histological grade (P < 0.0001) and overall survival (P = 0.0002). Additionally, MRP1 was determined as prognostic indicator independent of lymph node status using Cox proportional-hazards regression multivariate analysis (P = 0.0216). No relations between MRP2 and clinicopathologic features were observed. We have found that P-glycoprotein and MRP1 are expressed in highly aggressive canine mammary tumors and are related with poor prognosis. Our results suggest that they may play a significant role in the course of canine mammary cancer progression and be promising candidate markers for a validation study on therapy outcome.

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Salgado, B. , Nonogaki, S. , Soares, L. , Akamatsu, A. , Silva, C. , Anacleto, T. , Malagó, R. , Rocha, R. , Gärtner, F. and Rocha, N. (2015) Expression of Multidrug Resistance ATP-Binding Cassette (ABC) Transporters in Canine Mammary Tumors. Advances in Breast Cancer Research, 4, 77-85. doi: 10.4236/abcr.2015.43009.

Conflicts of Interest

The authors declare no conflicts of interest.


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