Mammary adenocarcinoma in a male squirrel monkey (Saimiri sciureus)

A nodule was identified within the right mammary gland of a 16-year-old male squirrel monkey (Saimiri sciureus). The mass was excised and diagnosed as a mammary adenocarcinoma. The monkey developed congestive heart failure 1.5 years later and was euthanatized. At necropsy, a subcutaneous mass was found in the right axillary region. Histologically, the mass was identified as a lymph node whose architecture was effaced by neoplastic cells resembling those of the mammary tumor. Metastasis to internal organs was not observed. This is the first reported case of a mammary tumor in a New World primate and the only known case of mammary cancer in a male nonhuman primate.     

Apocrine adenocarcinoma of possible sweat gland origin in a male rabbit

A five-year-old, male crossbreed rabbit was referred for acute caudal abdominal swelling. On physical examination, the rabbit was slightly depressed and showed an enlarged subcutaneous cyst in the caudal abdomen and an adjacent small, ulcerated solid mass. A drainage tube was placed in the cystic area, and surgical resection of the solid mass was performed. The histopathological diagnosis of the mass was apocrine adenocarcinoma. To the authors' knowledge, this report describes the first case of spontaneous apocrine adenocarcinoma of possible sweat gland origin in a male rabbit.     

Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas

In the present study, 13 clinical cases of canine mammary adenocarcinoma were evaluated in order to understand the effect of Tarantula cubensis extract (TCE) on tumor tissue. Punch biopsies were taken from the tumors before treatment with TCE. Subcutaneous injections of TCE were administered three times at weekly intervals (3 mL per dog). Between days 7 and 10 after the third injection, the tumor masses were extirpated by complete unilateral mastectomy. Pre- and post-treatment tumor tissues were immunohistochemically assessed. The expression of B-cell lymphoma 2 (Bcl-2) was found to be higher in pre-treatment compared to post-treatment tissues (p < 0.01) whereas Ki-67 expression was lower in post-treatment tissues (p < 0.01). No significant differences in fibroblast growth factor or vascular endothelial growth factor expression were observed between pre- and post-treatment tissues (p > 0.05). The apoptotic index was determined to be low before treatment and increased during treatment. These results suggest that TCE may be effective for controlling the local growth of canine mammary adenocarcinoma by regulating apoptosis.     

Spontaneous Mammary Adenocarcinoma in a Twelve-week-old Female Sprague-Dawley Rat

Spontaneous mammary adenocarcinoma was observed in a 12-week-old female SD rat. A movable mass in the right cervical region was found at 11 weeks of age, and the rat was sacrificed the following week. The mass was located in the vicinity of the right salivary gland and measured 38 mm × 26 mm × 16 mm in gross size. It was a firm whitish mass, with a cut surface that was also whitish in appearance. Histopathologically, neoplastic cells formed glandular structures that contained secreted eosinophilic material. Ultrastructurally, similar secreted material and lipid droplets were in the cytoplasm of the neoplastic cells. Immunohistochemically, the neoplastic cells were positive for cytokeratin 8, cytokeratin 18 and estrogen receptor α. Based on these findings, the tumor was diagnosed as a mammary gland adenocarcinoma, and we therefore conclude that this tumor type can occur spontaneously in female SD rats as young as 12 weeks of age.     

Diagnosis and Treatment of Anaplastic Mammary Carcinoma in a Sugar Glider (Petaurus breviceps)

A 9-year-old female sugar glider (Petaurus breviceps) was evaluated for a tissue mass near the marsupium. Ultrasonography identified a vascular mass originating from the right mammary gland. Fine-needle aspiration was suggestive of a malignant neoplasm. The glider was anesthetized and the tumor was removed, and this was followed by strontium-90 plesiotherapy to the tumor bed in an attempt to decrease local recurrence. Histopathology revealed an anaplastic mammary carcinoma. The glider was euthanized less than 14 days after the procedure owing to self-mutilation behavior of unknown etiology. This report is the first to describe the clinical presentation, diagnostics, therapeutics, and treatment response for a sugar glider with mammary neoplasia.     

Clinocopathologic and Immunohistochemical Findings of Multiple Genital Leiomyomas and Mammary Adenocarcinomas in a Bitch

A 13‐year‐old female Pointer dog was presented for evaluation of mammary tumours and bloody vaginal discharge at the Veterinary Teaching Hospital of Mehmet Akif Ersoy University, Faculty of Veterinary Medicine. On the history, owner complained of mammary tumours and bloody vaginal discharge. Three mammary tumours and lymphadenopathy at the mammary lymph nodes were observed at the clinical examination. A big, firm, palpable mass was found in the abdominal cavity. Vaginal cytology revealed numerous pleomorphic and anaplastic cells. Abdominal ultrasonography demonstrated a large mid‐abdominal mass at the distal part of the left uterine horn. Also multiple masses in the cervix and vagina were found. Because of the poor prognosis and the desire of the owner, the bitch was killed. At the necropsy numerous masses were seen at the vagina and cervix and one big mass seen at the left cornu uteri. Histopathological diagnosis was leiomyoma. Multiple metastases of mammary tumours were seen at the lungs. Histopathologically, mammary tumours were diagnosed as complex type tubulopapillary adenocarcinoma. The objectives of this study were to measure the proliferation indices in canine complex type mammary adenocarcinoma and genital leiomyomas using immunohistochemical detection of Ki‐67 and proliferating cell nuclear antigen to determine the relationship of these antigens to clinical and pathologic variables; and to examine the immunoreactivity of these tumours with different markers. Pan‐cytokeratin and S100 were negative, desmin and glial fibriler acidic protein were slight positive and the other markers (carsinoembryogenic antigen, proliferating cell nuclear antigen, vimentin, smooth muscle actin, p53, fibronectin, Ki67) were found strong positive at the genital tumours. Only desmin were negative; the other markers were strong positive at the mammary tumours.     

Salivary Gland Adenocarcinoma in a Domestic Rabbit (Oryctolagus cuniculus)

A 2.4 kg, 7-year-old, female Rex rabbit was presented with a 4-month history of a left-sided head tilt, difficulty in mastication, lethargy, and chronic wasting. Diagnostic testing of the patient revealed a severe heterophilic leukocytosis and radiographic images of the skull radiographs indicated irregularity of the left tympanic bulla. A computed tomographic scan highlighted a heterogeneously contrast-enhancing mass, ventral and rostral to the left tympanic bulla, with contrast enhancement of the meninges on the left, consistent with an aggressive neoplasm. The patient was euthanized and the mass was identified as a salivary gland adenocarcinoma. The gland of origin is suspected to be the left parotid, owing to its location and close association with normal parotid tissue. To the authors' knowledge, this is the first report of a salivary gland adenocarcinoma in a domestic rabbit. A computed tomography (CT) scan and histopathology examination were useful modalities for identifying the neoplasm in this case.     

Mammary gland adenocarcinoma in a mandrill (Mandrillus sphinix).

A 22-year-old female mandrill (Mandrillus sphinix) with continuously growing mass at the right mammary gland area was found dead, and a postmortem examination was performed. At necropsy, an elevated firm subcutaneous mass about 5 cm in diameter was present at the right mammary gland area. Axillary, mediastinal, and tracheobronchial lymph nodes were enlarged 2 to 4 times their normal sizes. Numerous metastatic foci 2 to 5 mm in diameter were scattered in the lung. Histologically, the tumor was diagnosed as mammary gland adenocarcinoma. Metastasis to the regional lymph nodes and lung was also confirmed. This is the first reported case of a mammary gland tumor in mandrill in Asia.     

Isolation, sequence characterization, and tissue transcription profiles of two novel buffalo genes: INSIG1 and INSIG2

Insulin-induced genes (INSIGs) are recently discovered genes that are involved in the metabolism of cholesterol and lipogenesis in animal tissues. In this study, two INSIG genes (INSIG1 and INSIG2) were isolated and characterized in 11 buffalo. The full-length coding sequence (CDS) of the buffalo INSIG1 consists of 831 bp which encodes a 276 amino acid protein with molecular mass 29.55 kD. And the INSIG2 CDS is 678 bp in length which encodes a 225 amino acid protein with molecular mass 24.87 kD. No polymorphisms were found in the CDSs of the buffalo INSIGs, but seven and two nucleotide differences were found in the CDSs between buffalo and other bovine species. Phylogenetic analyses based on the INSIG amino acid sequences showed that buffalo was grouped with other members in the Bovidae family. Four types of putative modification sites were detected in buffalo INSIG proteins. And two predicted microRNA target sites were found respectively in the CDSs of buffalo INSIG1 and INSIG2. The tissue expression analyses by quantitative PCR (qPCR) revealed that the buffalo INSIG1 was expressed in ten tissues tested. Among these tissues, the liver and mammary gland showed high expression levels. And the INSIG2 was only expressed in the brain, mammary glands, pituitary, abomasum, heart, and liver. Among these tissues, the mammary gland, brain, and pituitary demonstrated a high expression levels. These data provide the primary foundation for further insights into the buffalo INSIG genes.     

A case of adenocarcinoma of the endometrium extending into the leiomyoma of the uterus in a rabbit

In a pet rabbit, 2 tumor masses one on each horn were macroscopically seen in the wall of the uterus. On light microscopic examination, the right horn mass consisted of an admixture of neoplastic epithelial and mesenchymal element. The epithelial element was composed of neoplastic epithelial cells with numerous mitotic figures and formed varied sizes of acini, glandular, and solid structures. The tumor was diagnosed as an adenocarcinoma of the endometrium. The mesenchymal element was composed of well-differentiated smooth muscle cells and was diagnosed as a leiomyoma. While adenocarcinoma cells formed a protrusive mass in the uterine lumen, they also showed an extension into the leiomyoma of the myometrium. By immunohistochemistry, adenocarcinoma stained positive for cytokeratin (MNF116) and leiomyoma stained positive for smooth muscle actin, showing a substantial difference in the cytological nature of these tumor cells. The results may give a further evidence supporting the narrative of the tumor development that an adenocarcinoma of the endometrium extended into leiomyoma of the uterus. To the author's knowledge, this is the first report describing this type of combination of two independent tumors in a pet rabbit.     

Cellular proliferative and telomerase activity in canine mammary gland tumors

In canine mammary tumors, we examined the telomerase activity, proliferative activity by proliferative cell nuclear antigen (PCNA) immunohistochemistry, and percentage of apoptotic cells by the deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. The relationship between these measures and histopathologic malignancy was also investigated. PCNA index was highest in malignant tumors (adenocarcinoma: 27.0%; malignant mixed tumor: 15.7%), followed by benign tumors (adenoma: 4.4%; benign mixed tumor: 5.3%), hyperplasia (2.1%), and normal mammary gland (0.9%). In adenoma and adenocarcinoma, papillary and solid types showing higher cellularity tended to have higher PCNA indices than did cystic and tubular types. Although the TUNEL index was <1% in all cases, the relationship between this measure and histopathologic diagnosis showed the same tendency as observed in PCNA immunostaining. Telomerase activity was detectable in all adenomas, benign mixed tumors, and adenocarcinomas examined. In contrast, all normal mammary glands, hyperplasias, and malignant mixed tumors were negative for telomerase. Relative telomerase activity (RTA) of adenocarcinoma (56.5) was significantly higher than that of adenoma (27.8) and benign mixed tumor (33.9), and a significant positive correlation (P < 0.001) was noted between RTA and PCNA index. No significant correlations were noted between either PCNA or TUNEL index and clinical features such as metastasis and tumor diameter. PCNA index and telomerase activity may be useful markers for judging malignancy of canine mammary tumors.     

Carcinoma of the mammary gland in a mare

A 20‐year‐old Quarter Horse mare was presented with a firm, nonpainful swelling near the axial margin of the left mammary gland. Ultrasound examination of the mass revealed a 35 mm poorly encapsulated, homogeneous mass within the parenchyma of the left mammary gland. Using histopathology and immunohistochemistry, the mass was diagnosed as a mammary carcinoma and showed positivity for cytokeratin 18 (CK18), vimentin and α‐smooth muscle actin. Additionally, the mRNA expression level of the oncogene cMyc did not show a significant upregulation, whereas p53, a well‐known tumour suppressor gene in breast cancer, was significantly reduced in comparison with healthy equine mammary gland tissue. To the authors' knowledge, this is the first report of a significant downregulation of p53 expression in a mammary carcinoma of a mare.     

Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.     

Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines

There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. The stem cell-like properties of spheres derived from canine mammary tumors remain largely elusive. We attempted to induce sphere formation using four cell lines of canine mammary adenocarcinoma, and characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp-derived spheres showed predominantly CD44⁺CD24⁻ population, higher expression of stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to doxorubicin compared with the CHMp-derived adherent cells. Xenograft transplantations in nude mice demonstrated that only 1 × 10⁴ sphere cells were sufficient for tumor formation. Use of the sphere assay on these sphere-derived tumors showed that sphere-forming cells were present in the tumors, and were maintained in serial transplantation. We propose that spheres derived from canine mammary adenocarcinoma cell lines possess a potential characteristic of cancer stem cells. Spheres derived from canine mammary tumors could be a powerful tool with which to investigate novel therapeutic drugs and to elucidate the molecular and cellular mechanisms that underlie tumorigenesis.     

Genetic variations of BRCA1 and BRCA2 genes in dogs with mammary tumours

Mammary tumours are the most common tumour type in female dogs. The formation of the mammary tumours is multifactorial but the high incidence of tumour disease in certain canine breeds suggests a strong genetic component. BRCA1 and BRCA2 are the most important genes significantly associated with mammary tumours. The aim of this study was to determine the association between the variations of these two genes and canine mammary tumours. 5′-untranslated region, intron 8 and exon 9 of BRCA1 and exons 12, 24, 27 of BRCA2 were sequenced in order to detect the genetic variations. In addition to six previously identified polymorphisms, six novel single nucleotide polymorphisms (SNPs) were detected. Five of the coding SNPs were synonymous and three of them were non-synonymous. The comparison of the sequences from 25 mammary tumour bearing and 10 tumour free dogs suggested that the two SNPs in intron 8 and exon 9 of BRCA1 and two SNPs in exon 24 and exon 27 of BRCA2, which are firstly identified in this study, might be associated with mammary tumour development in dogs. Especially one SNP in exon 9 of BRCA1 and one SNP in exon 24 of BRCA2 were found to be significantly associated with canine mammary tumours.     

ErbB2 copy number gain is associated with adverse outcome in canine mammary carcinoma

Copy number gain (CNG) and/or protein overexpression of ErbB2 have been observed in human breast cancer patients and are associated with poor prognosis. Similarly, ErbB2 overexpression has also been observed in canine mammary carcinoma; however, data on ErbB2 copy number is limited. The purposes of this study were to evaluate ErbB2 copy number in dogs with mammary carcinoma and to investigate associations of ErbB2 CNG with ErbB2 expression, histological and clinical characteristics, and survival. DNA samples were isolated from 59 formalin-fixed paraffin-embedded canine mammary gland tissues (34 carcinoma, 14 adenoma, and 11 normal). Using a digital PCR assay, the ErbB2 copy number in these samples was determined as compared to a reference gene on canine chromosome 8. ErbB2 CNG was detected in 14/34 (41%) carcinomas and 2/14 (14%) adenomas. ErbB2 overexpression was observed in 3/34 (9%) carcinomas but not in adenomas. Neither ErbB2 CNG nor ErbB2 overexpression were detected in the normal controls. There was no significant association of the ErbB2 CNG with histological and clinical characteristics such as age, neutered status, histological grade, tumor size, lymph node involvement, distant metastasis, and clinical stage in the dogs with mammary carcinoma. The presence of ErbB2 CNG, but not ErbB2 overexpression, was significantly related to the shorter overall survival. These findings suggest that ErbB2 CNG is a prognostic factor in dogs with mammary carcinoma.     

DIAGNOSIS AND SURGICAL TREATMENT OF A TRANSITIONAL CELL CARCINOMA IN THE BLADDER APEX OF A PET RABBIT (ORYCTOLAGUS CUNICULUS)

A 6-year-old, 1.9-kg female spayed lop-eared European rabbit (Oryctolagus cuniculus) was evaluated for acute hematuria and inappropriate urination and defecation of less than 12-hours duration. Abdominal ultrasonography revealed a suspected bladder mass. Ultrasound-guided cystocentesis was performed and the results of the urinalysis were unremarkable. An abdominal exploratory surgery revealed a nodular cystic mass at the cranial ventral apex of the bladder wall which measured 0.5 cm × 0.5 cm. Based on histopathologic evaluation, excision of the neoplasm was complete and the mass was diagnosed as transitional cell carcinoma of the bladder. This case suggests that urinary bladder transitional cell carcinoma should be considered in pet rabbits presenting with similar clinical signs.     

Effectiveness of small interfering RNA (siRNA) against the Mcl-1 gene in a canine mammary gland tumor cell line

The effect of down-regulation of Mcl-1 expression by small interfering RNA (siRNA) against the canine Mcl-1 gene on apoptosis was investigated by transfecting CF33 (canine mammary gland tumor cell line) with siRNA using cationic liposomes. The siRNA against canine Mcl-1 increased the rate of apoptotic cells and decreased the numbers of viable cells. Further, sequence-specific down-regulation of Mcl-1 expression was measured by real time-PCR and Western blot analysis. The siRNA directed against the Mcl-1 gene reduced both the mRNA and protein expression in the CF33. Our study suggests the importance of Mcl-1 in canine mammary tumors for inducing apoptosis and reinforces using Mcl-1 as a putative therapeutic target in canine mammary gland tumor.