Breed-related differences in altered BRCA1 expression,phenotype and subtype in malignant canine mammary tumors |
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| Authors: | Keum-Soon Im Il-Hwan Kim Na-Hyun Kim Ha-Young Lim Jong-Hyuk Kim Jung-Hyang Sur |
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| Institution: | 1. Department of Veterinary Pathology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea;2. Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA;3. Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA;1. Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan;2. Veterinary Oncology, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan;3. Veterinary Surgery, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan;4. Veterinary Biochemistry, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan;1. Dept. Medicina y Cirugía Animal. Facultad de Veterinaria, Avda/Puerta de Hierro s/n, 28040, Universidad Complutense de Madrid, Spain;2. Dept. Fisiología Animal. Facultad de Veterinaria, Avda/Puerta de Hierro s/n, 28040, Universidad Complutense de Madrid, Spain;1. Small Animal Clinic, Veterinary Faculty, University of Ljubljana, Slovenia;2. Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, USA;3. Departments of Orofacial Sciences, Pathology and Radiation Oncology, University of California, San Francisco, USA;4. Departments of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA;6. Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, USA;1. Department of Animal Physiology, Veterinary Medicine School, Complutense University of Madrid, Madrid, Spain;2. Department of Animal Medicine, Surgery and Pathology, Veterinary Medicine School, Complutense University of Madrid, Madrid, Spain;1. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte CEP: 31270-901, MG, Brazil;2. Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte CEP: 31270-901, MG, Brazil;1. Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal;2. Instituto de Ciências Biomédicas de Abel Salazar, University of Porto, 4099-003 Porto, Portugal;3. CECAV, Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal;4. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal;5. ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal;6. CECA, University of Porto, Porto, Portugal |
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| Abstract: | BRCA1 is a high-penetrance breast cancer susceptibility gene and BRCA1-associated breast cancer has a high familial prevalence that is more common among certain populations of humans. A similar high prevalence also exists for canine mammary tumors (CMTs) and the objective of this study was to determine the breed-related differences in malignant CMTs. Comparative analyses of the expression of various prognostic factors for CMTs, including BRCA1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) were conducted on 139 malignant CMT cases from five breeds with the highest prevalence of CMTs in Korea.Significant breed-related differences were observed in the expression of BRCA1 (P = 0.003), histological grade (P = 0.038), and extensive lymphatic invasion (P = 0.042). The Shih Tzu breed had the highest proportion of dogs with malignant CMT and strong overexpression of BRCA1. Cytoplasmic and membranous expression of BRCA1 was associated with the ER negative (P = 0.004), PR negative (P = 0.046), and triple negative (ER, PR, and HER-2 negative; P = 0.016) phenotype and the basal-like molecular subtype (P = 0.019) in Shih Tzu dogs. Since these features are similar to BRCA1-related human breast cancer, dogs with BRCA1-associated CMT, particularly Shih Tzu dogs, may serve as a suitable spontaneous model, although additional molecular studies are needed. |
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