• Journal of Veterinary Clinics
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• v.27 no.3
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• pp.232-239
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• 2010

Two cell lines derived from spontaneous canine mammary gland tumors were established and characterized. Mammary gland tumors from 9 years old pug and 9 years old toy-poodle dogs were collected by aseptic surgical resection and primary culture was performed. The histopathologic examination of tumors revealed adenocarcinoma and complex carcinoma and two dogs died from metastasis of the tumors. The tumor cells were subcultured over 60 times for more than 1 year and morphological consistency maintained. Light microscopic examination, growth curve, doubling time calculation, xenotransplantation to female nude mice, immunohistochemistry for wide spectrum keratin, vimentin, $\alpha$-smooth muscle actin and cytokeratin 8 was performed for characterization. The cell lines exhibited polygonal, elongated cell shape and cytoplasmic bridge and doubling time of 47.1 hrs and 18.6 hrs, respectively. Subcutaneous xenotransplantation to nude mice of the cells produced localized palpable mass within 4 weeks in 4 of 5 and 5 of 5 nude mice, respectively. In immunohistochemical examination one cell line showed strong positive against wide spectrum keratin and cytokeratin 8 and the other cell line showed strong positive against smooth muscle actin and cytokeratin 8. Additional characterization would be possible by investigator's needs and the cell lines may be useful for in vivo and in vitro studies of canine mammary tumor and adjuvant therapies.

• Journal of Veterinary Clinics
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• v.26 no.6
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• pp.556-562
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• 2009

Skin tumors and mammary gland tumors have been shown to be the most common neoplasia in most of the strains of dogs. The risk for tumor development increases significantly with age and the prevalence and distribution are various according to individual tumors. The aim of this study is to classify histopathologically the skin and mammary gland tumors for recent two years, 2005 and 2006. A total of 128 skin and 240 mammary gland samples of dogs were selected that were submitted to National Veterinary Research and Quarantine Service and Kangwon National University from January 1, 2005 to December 31, 2006. The excised tissue were fixed in 10 percent neutral buffered formalin and processed routinely to paraffin wax. Sections were cut at $3{\mu}m$, stained with haematoxylin and eosin. The slides were examined based on the morphological criteria of M. H. Goldschmidt and W. Misdorp under a light microscope. The age of the dogs ranged from 1 to 19 years with a median of 8.7 years. The mean age of the skin and mammary gland tumors was 7.4 and 9.3 years. 47 (12.8%) were males and 259 (70.4%) were female with a male to female ratio of 0.18. Yorkshire terrier and maltese were more susceptible breeds, accounting for 44.3% of skin and mammary gland tumors. In skin tumors, epithelial, adnexal, and mesenchymal origin tumors were 18 (14.1%), 53 (41.4%), and 57 cases (44.5%), repectively. Among the epithelial, adenexal, and mesenchymal origin tumors, basal cell tumor (8.6%), sebaceous adenoma (15.6%), and histiocytoma (25.0%) were predominant in the incidence rate, respectively. In case of mammary gland tumors, 201 (83.8%) were benign and 39 (16.3%) were malignant with a benign to malignant ratio of 5.15. The most frequent mammary gland tumor was benign mixed tumor (35.0%) followed by mammary adenoma-complex type (31.7%).

• Journal of Veterinary Clinics
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• v.41 no.4
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• pp.215-222
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• 2024

An adult female dog was presented for evaluation of rapid growth of mammary gland masses. Complete blood count, serum biochemistry, and diagnostic imaging results were unremarkable. Fine needle aspirates of the mammary masses indicated mammary carcinoma characterized by large globoid cells with finely granular eosinophilic globules or Melamed-Wolinska-like bodies. A regional mastectomy was performed on the masses. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of mammary comedocarcinoma with nodal metastasis and distinct perivascular immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. Immunohistochemical examination confirmed the infiltration of CD3⁺ T and PAX5⁺ B lymphocytes. Flow cytometric analysis demonstrated tumor-infiltrating CD4⁺CD25⁺FOXP3⁺ regulatory T, CD8⁺ T, CD11b⁺ myeloid, and CD21⁺ B cells. Of note, paired flow cytometric analysis of peripheral blood and tumor tissues showed a preferential tumor infiltration of regulatory T and B cells. Approximately two months after the mastectomy, the tumor reoccurred at the surgery site. The dog died due to deteriorating conditions. We report a rare case of canine mammary comedocarcinoma, providing clinical, clinicopathologic, histologic, and immunophenotypic characteristics. Our case is valuable in providing a rationale for basic research that maps the immune landscape of mammary comedocarcinoma to identify key immune subsets for cancer progression.

• Korean Journal of Veterinary Service
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• v.47 no.3
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• pp.173-178
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• 2024

In this case study, we present a rare occurrence of simultaneous primary malignant neoplasms arising from the mammary gland and uterus in conjunction with pyometra and inguinal hernia. The subject, a 16-year-old intact mixed-breed dog, exhibited tubulopapillary carcinoma of the mammary gland with grade II malignancy and uterine leiomyosarcoma. Treatment involved partial mastectomy for the mammary carcinoma and ovariohysterectomy for the uterine leiomyosarcoma. Moreover, the inguinal hernia was concurrently repaired during the tumorectomies. The patient demonstrated positive postoperative progress over a span of two years, emphasizing the effectiveness of surgical intervention in managing the coinciding pathologies in an elderly canine. This unique co-occurrence of primary malignant neoplasms originating from distinct organ systems presents valuable insights into diagnostic approaches, disease characteristics, and surgical interventions in the realm of clinical oncology.

• Journal of Veterinary Science
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• v.22 no.5
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• pp.62.1-62.13
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• 2021

Background: Canine mammary gland tumor (MGT) is the most common cancer in aged female dogs. Although it's important to identify reliable metastasis or prognostic factors by evaluating related to cell division, adhesion, and cancer stem cell-related transcription factor (TF) in metastasis-induced canine MGT, but there are limited studies. Objectives: We aimed to identify metastasis prognostic factors and cancer stem cell-TFs in canine MGTs. Methods: Age-matched female dogs diagnosed with MGT only were classified into metastatic and non-metastatic groups by histopathological staining of MGT tissues. The mRNA levels of cancer prognostic metastasis molecular factors (E-cadherin, ICAM-1, PRR14, VEGF, HPRT1, RPL4 and hnRNP H) and cancer stem cell-related TFs (Oct4, Sox2, and Nanog) were compared between metastatic and non-metastatic canine MGT tissues using qRT-PCR analysis. Results: The mRNA levels of ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog in metastatic MGT group were significantly higher than those in non-metastatic MGT group. However, mRNA level of RPL4 was significantly lower in metastatic MGT group. Loss of E-cadherin and HPRT1 was observed in the metastatic MGT group but it was not significant. Conclusions: Consistent expression patterns of all metastasis-related factors showing elevation in ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog, but decreases in RPL4 levels occurred in canine MGT tissues, which was associated with metastasis. Thus, these cancer prognostic metastasis factors and TFs of cancer stem cells, except for E-cadherin and HPRT1, can be used as reliable metastasis factors for canine MGT and therapeutic strategy.

• Korean Journal of Veterinary Research
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• v.53 no.3
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• pp.185-187
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• 2013

An 11-year-old, toy poodle dog was presented with dermatologic lesions and mammary gland tumor (MGT) evaluation. A solitary, lobulated MGT (size $2.5{\times}3.5$ cm) was affecting the 5th left mammary gland. Firm, oval plaque skin lesions were present on the left dorsal carpal area. The skin lesions were alopecic and salivary staining. The dog had historical separation anxiety and excessive licking of skin lesions were observed. Based on the clinical and histopathologic examinations, MGT was diagnosed with mammary complex adenoma and the skin lesions were diagnosed with acral lick dermatitis. Behavior modification treatment using oral clomipramine was effective.

• Journal of Veterinary Clinics
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• v.40 no.2
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• pp.164-174
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• 2023

Canine splenic tumors (STs) are commonly diagnosed during imaging examinations, such as in X-ray and ultrasonography examinations, suggesting their higher prevalence, especially in older dogs. Despite this high prevalence, there are no effective treatment options for STs because of the difficulties in determining therapeutic targets. However, recently, the importance of microRNAs (miRNAs) has evolved owing to their ambivalent characteristics. Biomarkers and novel therapies using miRNAs have been well-studied in human cancer research compared to canine research, except for mammary gland tumors. Therefore, this study aimed to comparatively analyze miRNA expression profiles according to malignancy and biopsy sites to identify novel therapeutic and diagnostic targets. Tissue samples were collected directly from splenic tumor masses and immersed in RNAlater solution for further analysis. To investigate differentially expressed genes (DEGs) between tumor and normal tissues, we used RNA-seq and miRNA microarray analysis. Then, functional analysis based on DEGs was conducted to sort tumor-related DEGs. We found that cfa-miR-150 was upregulated in benign tumors, whereas cfa-miR-134 was upregulated in malignant tumors. Despite limited information on canine miRNAs, we identified two potential biomarkers for the differential diagnosis of STs.

• Korean Journal of Veterinary Research
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• v.53 no.2
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• pp.109-115
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• 2013

Cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumorinitiating cells. These cells possess the ability to self-renew and proliferate, and are thus able to form the tumor. In the present study cells that correspond to cancer stem cells in mammary and liver cancers in animals were identified by the expression of CD133, CD44, CK7, and OCT4 using immunochemistry. As a result, we found with CD133+ and CD44+ cancer stem cell-like phenotypes in mouse and canine hepatocellular carcinoma and canine mammary gland tumors. However, CK7+ and OCT4+ cells were not identified in animal mammary and liver cancer. CD133+ and CD44+ cells are wellknown stem cell lines and play key roles in development and metastasis in human cancer. These findings suggest that cancer stem cells are involved in animal tumorigenesis and may provide insight into mechanisms in cancer development as well as cancer diagnostics.

• Journal of Life Science
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• v.17 no.12
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• pp.1766-1770
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• 2007

We describe here a case of malignant mixed osteogenic tumor of the mammary gland with alveolar carcinomatous appreance. A firm, 2 to 2.5cm (in diameter) mass under the 5th nipple, showing the structure of extraosseous osteogenic sarcoma, was removed from the left 5th mammary gland of 12-year-old female dog. When investigated under the microscope, the osteoid material undergoing mineralization was surrounded by numerous scattered osteoblasts and a few osteoclastic cells throughout the osteoid tumorous stroma. The osteoid lesions were continuous with hypercellular myoepithelial cells of a very immature character with several mitotic figures. In addition, there were also carcinomatous tubules and alveoli, with invading cells into peripheral stroma, surrounded by myoepithelial cells in the mammary gland. In these lesions, emanating cords of tumor cells appear to be continuous with the myoepithelial cell layer of a duct. The presence of all these cell types suggests the existence of a common malignant origin, the stem cell being differentiated into epithelial carcinomatous and mesenchymal sarcomatous chondral and osteogenic tissues.

• Journal of Life Science
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• v.18 no.1
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• pp.16-22
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• 2008

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.