Prognostic impact of alterations in E-cadherin and P-cadherin expression in canine mammary tumors

Expression of cadherins has been correlated to the development and aggressiveness of epithelial neoplasms, however, in canine mammary tumors, their significance prognostic is uncertain. Due to this fact, the expression of the intracellular adhesion molecules E and P-cadherin and correlation with overall survival were analyzed in 25 canine mammary gland tumors. E-cadherin expression reduction was correlated with histological type, high histological grade, and overall survival rate. P-cadherin staining was higher in malignant tumors, unrelated to other clinicopathological features of aggressiveness. The results of this study suggest a relationship between lower expression of E and P-cadherin and worse prognostic in canine mammary tumors, including shorter overall survival.

Involvement of Nestin in the Progression of Canine Mammary Carcinoma

Nestin, a class VI intermediate filament protein, is known to be expressed in various types of human neoplasms, including breast cancer, and is associated with their progression. However, its expression and role in canine mammary tumors remain unknown. We analyzed nestin expression in canine mammary tumors using in situ hybridization and immunohistochemistry. We also investigated its role in a canine mammary carcinoma cell line using RNA interference. Nestin expression was not observed in luminal epithelial cells of any of the 62 cases of benign mammary lesions examined, although myoepithelial cells showed its expression in most cases. In 16/50 (32%) primary mammary carcinomas and 6/15 (40%) metastases of mammary carcinomas, cytoplasmic nestin expression was detected in luminal epithelial cells. In luminal cells of primary mammary carcinomas, its expression was positively related to several pathological parameters that indicate high-grade malignancy, including histological grading ( P < .01), vascular/lymphatic invasion ( P < .01), Ki-67 index ( P < .01), and metastasis ( P < .05). Immunohistochemistry revealed that nestin expression was related to vimentin expression in mammary carcinomas ( P < .01). This relationship was confirmed using reverse transcription-quantitative polymerase chain reaction using 9 cell lines derived from canine mammary carcinoma ( P < .01). Finally, nestin knockdown in canine mammary carcinoma cells using small interfering RNA inhibited cell proliferation and migration based on WST-8, Boyden chamber, and cell-tracking assays. These findings suggest that nestin may at least partially mediate these behaviors of canine mammary carcinoma cells.

Immunohistochemical Analysis of Na+/K+-ATPase and Bone Morphogenetic Protein-2 Expressions in Both Parenchymal and Stromal Cells from Benign and Malignant Canine Mammary Tumors

Canine mammary tumors are the most common type of dog tumor, and they are similar to human breast tumors. Na+/K+-ATPase is a common plasma membrane ion pump with important physiological and pathophysiological functions. In mammary tumors, the tumor microenvironment was composed of a heterogeneous population of tumor cells and nearby endogenous stromal cells. Bone morphogenetic proteins (BMPs) regulate fetal development, tissue homeostasis and differentiation, and a variety of cellular functions. The purpose of this study is to examine the immunohistochemical expression of Na+/K+-ATPase and BMP-2 in tumoral and stromal cells from benign and malignant canine mammary tumors. In this study, ten benign and ten malignant mammary tumors from the archives of the Department of Pathology were used, with five normal breast tissues serving as controls. The results of the revealed that tumors had higher levels of Na+/K+-ATPase and BMP-2 expressions than normal mammary tissue. While both markers were expressed negatively or mildly in benign tumors, they increased significantly in malignant tumors. Both Na+/K+-ATPase and BMP-2 are expressed by tumoral and stromal cells in canine mammary tumors. When compared to compared to BMP-2, Na+/K+-ATPase expression was found to be more severe. This study found that Na+/K+-ATPase and BMP-2 can be used as markers of malignancy in canine mammary tumors and that stromal cells also play an important role in tumor progression. These findings also indicated that Na+/K+-ATPase and BMP-2 may be used for early diagnosis or as a potential target for treatment of canine and human breast tumors in the future.

Veterinary approaches to canine mammary tumors and knowledge of the consensus statement in Brazil

Mammary gland tumors are one of the most commonly diagnosed tumors in female dogs, with a reported prevalence ranging from 26 to 73% in Brazil. In recognition of the importance of these tumors veterinary researchers and clinicians in Brazil produced the first consensus statement regarding canine mammary tumors in 2010. The intention was to establish criteria for diagnosis, prognosis, and treatment. This study evaluated the methods of prevention, diagnosis, treatment, and determination of prognosis used by veterinarians in Brazil, and sought to quantify the number of veterinarians who were aware of the consensus statement. One hundred and three veterinary clinics participated in the study, 87.37% of which recommend early neutering as a preventative treatment for mammary tumors. For diagnosis, 100% of these use laboratory testing, 94.17% perform chest radiography, 78.64% incisional biopsies, 44.66% cytological analysis, and 13.59% immunohistochemical analysis. The most common surgical procedure is unilateral mastectomy (72.81%), and chemotherapy is performed in 49.51% of the clinics. Of the 103 clinics, 66.01% were aware of the consensus. Although knowledge of the consensus statement is widespread among veterinarians in Brazil, not all its recommendations are being followed. Preventive actions for canine mammary tumors are well established in most parts of the country. However, the consensus statement has had little influence on informing prognostic and therapeutic approaches, with a poor uptake of surgical removal of lymph nodes and immunohistochemical examination.

MicroRNA-21 Expression, Serum Tumor Markers, and Immunohistochemistry in Canine Mammary Tumors

Background: Canine mammary tumors (CMTs) are one of the most common malignancies in dogs and are associated with significant mortality. Serum tumor markers and non-coding microRNAs have recently gained widespread popularity in human oncology studies. We aimed to investigate the expression of microRNA-21 (miR21), changes in serum tumor markers (CEA and CA 15-3), and immunohistochemistry in CMTs diagnosed by clinical examination, radiology, and histopathology. This study enrolled 17 female dogs: 10 with mammary tumors and seven controls without tumors. Blood samples were collected to measure miR-21, CEA, and CA 15-3, and histological samples were prepared for histological grading and immunohistochemistry. Results: CA 15-3 was elevated in all animals, whereas CEA levels showed no change compared with controls. miR-21 was upregulated 12.84-fold in animals with CMT. The most frequently recorded CMT was mixed type. Myoepithelial cells were identified by P63 immunoreactivity, but not SMA. High expression of miR-21 was observed with positive vimentin immunoreactivity, indicating a mesenchymal origin of the tumor cells. Conclusion: The present study showed that miR-21 was elevated to a greater extent than CA 15-3 (12.84-fold vs. threefold). Mixed-type tumors with positive vimentin immunoreactivity showed the highest miR-21 levels. These findings support the hypothesis that miR-21 may be a more sensitive, noninvasive indicator for CMT.