Breed-related differences in altered BRCA1 expression, phenotype and subtype in malignant canine mammary tumors.
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.
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.
Keum-Soon
KS
Im
Il-Hwan
IH
Kim
Na-Hyun
NH
Kim
Ha-Young
HY
Lim
Jong-Hyuk
JH
Kim
Jung-Hyang
JH
Sur
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D004283:Dog Diseases / Q000145:classification / Q000453:epidemiology / Q000378:metabolism*; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018734:Genes, erbB-2 / Q000502:physiology; D015674:Mammary Neoplasms, Animal / Q000145:classification / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D056910:Republic of Korea / Q000453:epidemiology
D019313:BRCA1 Protein; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone