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.
Bibliographical noteFunding Information:
The authors thank Ms. Rae-Hwa Jang for her excellent technical assistance and the participating private veterinary clinics for providing access to tissue samples of canine mammary tumors. This report represents a part of a PhD Thesis by Il-Hwan Kim. The research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) and was funded by the Ministry of Education, Science and Technology (2011-0021337).
- Basal-like subtype
- Mammary tumors
- Shih Tzu