Feline Mammary Carcinoma: Past, Present and Future
The Pathology Lab at CIISA/FMV has been conducting efforts towards the understanding of the molecular mechanisms underlying the feline mammary carcinoma (FMC). So far, the detection and quantification of three novel molecular biomarkers (HER2, SDF-1, CXCR
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Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisbon, Portugal [email protected] 2 Research Center for Biosciences & Health Technologies, Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias (ULHT), Campo Grande 376, 1749-024 Lisbon, Portugal
Abstract. The Pathology Lab at CIISA/FMV has been conducting efforts towards the understanding of the molecular mechanisms underlying the feline mammary carcinoma (FMC). So far, the detection and quantification of three novel molecular biomarkers (HER2, SDF-1, CXCR4) were optimized in tumor tissue samples and sera, and their clinical usefulness was also validated. In parallel, six FMC immunophenotypes were reported and characterized, showing similar clinicopathological features to the ones described in human breast cancer patients. In a prospective study, our group reported that queens showing triple negative basallike or HER2-positive mammary carcinoma subtypes are associated to shorter overall survival, contrasting with queens presenting luminal A/luminal B and triple negative normal-like molecular subtypes. We also demonstrated that the frequency of HER2 overexpression in FMC is similar to what is reported in women (about 30%), although no gene amplification was detected. More recently, studies on the role of CXCR4-SDF-1 axis and of miRNAs in FMC were performed in order to explore their role in oncogenesis and to validate new diagnostic/prognostic serum biomarkers. Finally, the antitumor activity of new TK inhibitors is under evaluation, using FMC HER2-positive and HER2-negative cell lines towards the support of new specific molecular therapies. Keywords: Feline mammary carcinoma · Biomarkers · Diagnosis · Prognosis · HER2 · SDF-1/CXCR4 axis
1 Introduction Cats are popular companion animals in Europe and in the USA (Downes et al. 2009; Murray et al. 2010; Murray et al. 2015). In 2011, the estimated UK cat population was 10 114 764, which was quite similar to the estimated dog population – 11 599 824 A. Gameiro and F. Almeida—Contributed equally to the work. © Springer Nature Switzerland AG 2020 A. Freitas Duarte and L. Lopes da Costa (Eds.): Advances in Animal Health, Medicine and Production, pp. 419–435, 2020. https://doi.org/10.1007/978-3-030-61981-7_23
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(Murray et al. 2015). In parallel, in the USA, data from 2012 indicates that there were approximately 74 059 000 cats and 69 926 000 dogs (American Veterinary Medicine Association 2012). Cancer in companion animals is one of the major causes of death and morbidity, and at least 4 million cats develop this disease every year. The incidence of Feline Mammary Carcinoma (FMC) is increasing, probably due to a humanized lifestyle, an unbalanced diet and unregulated environmental factors. Moreover, better prevention and efficient treatment of infectious diseases also contribute to this reality. Despite this scenario, few studies have been published reporting the diagnostic, therapy and prognostic assessment of FMC
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