• Korean Journal of Veterinary Research
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• v.37 no.4
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• pp.843-854
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• 1997

Sixteen mammary gland tumors were collected from Seoul National University and Kangwon National University. The average age of the bitches with mammary gland tumor was 10 years. Total 17(60.7%) out of 28 tumor masses observed in 4th and 5th glands. Classification of these tumors according to Hampe and Misdorp were simple adenoma, complex adenoma, benign mixed tumor, papillary adenocarcinoma, solid adenocarcinoma and malignant mixed tumor. Immunohistochemical reaction of the intermediate filaments against normal canine mammary gland showed as followed; anti-cytokeratin 18 was strong and anti-cytokeratin 14 was moderate to the luminal epithelium. Anti-cytokeratin 14 and anti-pancytokeratin to the myoepithelium were showed strong, but anti-vimentin was weak in reactivity. Anti-vimentin to the interstitial cells was represented strong reactivity. The origin of cartilage in mixed tumor of canine mammary gland was studied immunohistochemically with antibodies against intermediate filament. In mammary gland mixed tumors, cartilage tumor tissues were surrounded with the irregularly demarcated three zones composed of adjacent star shaped cells in myxoid areas, proliferative spindle shaped cells and basal located proliferated cells. From basal proliferated cells to star shaped cells, the immunohistochemical reactivity of myoepithelium specific anti-pancytokeratin was decreased gradually and the reactivity of interstitial cell specific anti-vimentin was increased gradually. Based on these immunohistochemical staining patterns, we suggested that the origin of cartilagenous components in canine mammary gland mixed tumor is most likely to the proliferation and metaplsia of myoepithelium.

• Korean Journal of Veterinary Research
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• v.62 no.1
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• pp.9.1-9.6
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• 2022

Canine mammary gland tumors are the most common neoplasms in intact female dogs. Approximately half of all mammary tumors are malignant, and there is a risk of metastasis, which is associated with a poor prognosis. This study was to evaluate the prognostic factors of canine mammary gland tumors and the risk factors associated with the development of malignant tumors. From 2014 to 2020, 60 dogs with mammary gland tumors that underwent surgical treatment were evaluated in this retrospective study. Tumor size, TNM stage, and histopathological results were prognostic factors for 2-year survival after surgery. Every 10 mm increase in tumor size, increased the risk of death within 2 years after surgery 1.213 times. Dogs with TNM stage IV or V had 8.667 fold risk of death within 2 years after surgery. The 2-year survival rate for dogs with benign tumors was 90.2% and for malignant tumors was 67.3%. Tumor size is the most important prognostic factor for canine mammary gland tumors. As tumor size increased by 10 mm, the risk for development of malignant tumors increased by 1.487 times. Tumors larger than 30 mm are highly likely to be malignant, and metastatic evaluation and wide resection should be considered.

• Journal of Veterinary Clinics
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• v.38 no.6
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• pp.274-278
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• 2021

An 11-year-old, intact female, Miniature Poodle presented with an abdominal mass. The abdominal mass was located around the right fifth mammary gland. The surgically removed mammary mass was subjected to histopathological examination. Based on the microscopic interpretation, a final diagnosis of an intermediate grade infiltrative mammary comedocarcinoma was established. Computed tomography for metastasis evaluation after surgical resection of the tumor showed enlarged right medial iliac and right inguinal lymph nodes, and a micronodule in the accessory lung lobe, suggesting metastasis of the mammary gland tumor. Doxorubicin, a chemotherapeutic drug, was administered six times at three week intervals. However, despite chemotherapy, the masses around the fourth and fifth mammary gland on the right side enlarged in size, and the treatment was discontinued at the request of the owner. The anticancer response to mammary comedocarcinoma is poor and the patient is in hospice management. This is the first attempt to treat a case of canine mammary comedocarcinoma in South Korea.

• Journal of Veterinary Science
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• v.25 no.1
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• pp.1.1-1.15
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• 2024

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion: In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.

• Journal of Veterinary Science
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• v.21 no.2
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• pp.23.1-23.10
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• 2020

The identification of biomarkers that distinguish diseased from healthy individuals is of great interest in human and veterinary fields. In this research area, a metabolomic approach and its related statistical analyses can be useful for biomarker determination and allow non-invasive discrimination of healthy volunteers from breast cancer patients. In this study, we focused on the most common canine neoplasm, mammary gland tumor, and herein, we describe a simple method using ultra-high-performance liquid chromatography to determine the levels of tyrosine and its metabolites (epinephrine, 3,4-dihydroxy-L-phenylalanine, 3,4-dihydroxyphenylacetic acid, and vanillylmandelic acid), tryptophan and its metabolites (5-hydroxyindolacetic acid, indoxyl sulfate, serotonin, and kynurenic acid) in canine mammary cancer urine samples. Our results indicated significantly increased concentrations of three tryptophan metabolites, 5-hydroxyindolacetic acid (p < 0.001), serotonin, indoxyl sulfate (p < 0.01), and kynurenic acid (p < 0.05), and 2 tyrosine metabolites, 3,4-dihydroxy-L-phenylalanine (p < 0.001), and epinephrine (p < 0.05) in urine samples from the mammary gland tumor group compared to concentrations in urine samples from the healthy group. The results indicate that select urinary tyrosine and tryptophan metabolites may be useful as non-invasive diagnostic markers as well as in developing a therapeutic strategy for canine mammary gland tumors.

• Korean Journal of Veterinary Service
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• v.37 no.4
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• pp.313-317
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• 2014

A bitch was presented for investigation of the mass in left 5th mammary gland. The partial mastectomy was performed and submitted for the histopathological diagnosis. The mammary mass was firm and white colored. The cut surface was separated with several lobules and developed vessels. The central area of the mass formed the cavity filled with inflammatory exudates. The dominant component of the tumor was the bundles of spindle-shaped cells. Some tumor cells possessed atypical nuclei and were arranged in a solid nest. Cysts were microscopically composed of hemorrhage, necrosis, and exudates, partially surrounded by tumor cells and granulation tissues. Histopathologically, the mammary mass revealed spindle cell carcinoma. The bitch made a complete recovery following the mastectomy. This case was a rare mammary spindle cell carcinoma in a dog.

• Journal of Veterinary Clinics
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• v.11 no.2
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• pp.567-572
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• 1994

A 14-year-old virgin, female Yorkshire Terrier showed enlarged abdomen after udderectomy was diagnosed with canine mammary gland tumor accompanied with hydrometra. Gross findings appeared a white-yellowish $l0{\times}7{\times}7cm sized solid mass containing cysts filled with various colored mucoid fluids in the udder. Both uteri were distended greatly with white-yellowish watery fluids and their serosal surfaces were translucent. Characteristic micyoscopic findings in the mass of the udder showed great expansion of the mammary lobule and stroma and complete replacement of the glandular elements by prolifaration of myoepithelial cells. The mucosa of the uterus showed severe atrophy of the uterine epithelium.

• Journal of Life Science
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• v.31 no.2
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• pp.248-255
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• 2021

Mammary gland tumors are one of the most common cancers in female dogs, and there are various types of cells depending on the tumor type. Complex carcinoma consists of a combination of luminal epithelial and myoepithelial cells with intra-tumoral heterogeneity. However, the origins of these tumor cells and their effects on the malignancies of tumors have not been identified. Recently, it has been reported that cancer stem cells, identified in several types of human tumors, are involved in tumor heterogeneity and may also contribute to malignancies such as tumor recurrence and metastasis. Interestingly, cancer stem cells share several abilities of self-renewal and cell differentiation into multiple types of cancer cells, but they have abnormal genetic mutation and signal transduction pathways to regulate the maintenance of stem cell characters. Moreover, it is known that these cell populations contribute to cell metastasis as well as cell resistance against chemo- and radio-therapeutics that promote tumor recurrence. The existence of cancer stem cells might explain the intra-tumoral heterogeneity and cancer aggressiveness during tumorigenesis in canine mammary gland tumors. This review summarizes the characteristics and types of canine mammary gland tumors, the definition of tumor stem cells, methods of isolation, and clinical significance.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6415-6421
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• 2012

Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.

• Journal of Veterinary Clinics
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• v.19 no.2
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• pp.195-198
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• 2002

To identify mutations in exons 5 to 8 of the p53 tumor suppressor gene, we have analysed in 12 spontaneous canine tumors. In a malignant mast cell tumor, a 1 base pair alteration AGT $\longrightarrow$AGC (silent point mutation, serine) in codon 249 in exon 8 was detected. And the mammary gland adenocarcinoma was found to have a mis-sense point mutation (CCT $\longrightarrow$ TCT) in codon 285 in exon 8.