Reduction of phosphorylated signal transducers and activator of transcription-5 expression in feline mammary carcinoma.

Signal transducers and activators of transcription (STAT) is a family of transcription factors involved in various normal physiological cellular processes. Moreover, STATs have been recently identified as novel therapeutic targets for various human tumors. STAT3, STAT5a, and STAT6 have been suggested to be involved in tumorigenesis in human breast cancer. Owing to the similarity between feline mammary carcinomas (FMCs) and human breast cancers, these factors may play an important role in FMCs. However, studies on the expression of STATs in animal tumors are limited. Therefore, in this study, we aimed to characterize the expression of total STAT5 (tSTAT5) and phosphorylated STAT5 (pSTAT5) in FMCs, feline mammary adenomas, non-neoplastic proliferative mammary gland lesions, and normal feline mammary glands using immunohistochemistry. High expression of tSTAT5 was observed in the cytoplasm of all the samples assessed in this study. Moreover, high expression of tSTAT5 was observed in the nucleus; however, its levels varied depending on the lesion. The percentage of pSTAT5-nuclear positive cells varied among normal feline mammary glands (40.1 ± 25.1%), and non-neoplastic lesions, including mammary hyperplasia (43.2 ± 28.6%) and fibroadenomatous changes (18.0 ± 13.6%). Moreover, the percentage of pSTAT5-nuclear-positive cells in feline mammary adenomas was 24.5 ± 19.2%, which was significantly reduced in feline mammary carcinomas (2.4 ± 5.6%), regardless of histopathological subtype. This study suggests that decreased STAT5 activity may be involved in the development and malignant progression of feline mammary carcinomas.

Feline uterine carcinosarcoma infiltrated with osteoclast-like giant cells.

A 12-year-old female Himalayan cat underwent an ovariohysterectomy to remove an intra-abdominal mass. Histologic examination using immunohistochemical staining revealed that the mass was comprised of epithelial and mesenchymal components. Within the lesion, multinucleated giant cells (MGCs) were observed diffusely. MGCs were positive for vimentin and Iba-1 and negative for cytokeratin AE1/AE3 and CD204. In addition, MGCs were negative for Ki-67, indicating nonneoplastic cells. Osteoclast-like MGC (OLMGC) phenotype with tartrate-resistant acid phosphatase positivity was also seen. These findings suggested that the uterine tumor was carcinosarcoma with OLMGCs. Uterine tumors in humans, such as leiomyosarcoma and carcinosarcoma, with OLMGC infiltration, are well-known pathologic entities; however, they are rare in animals and to our knowledge, have not been previously reported in cats.

Extraskeletal osteosarcoma associated with two different types of synthetic fibers derived from a surgical swab in a dog.

A 10-year-old spayed female Japanese Shiba Inu had an intraperitoneal mass that was excised surgically. The central area of the mass was composed of osteoblast-like neoplastic cells, osteoid, macrophages, and numerous fibers. The neoplastic cells showed nuclear atypia and many mitotic figures. Therefore, the central area of the mass was diagnosed as an extraskeletal osteosarcoma. The peripheral area of the mass was granuloma tissue with numerous fibers. The neoplastic and granuloma area included two types of fibers, which were identified as rayon and polyester by their morphological and staining characteristics. These fibers were consistent with those of commercial surgical swab, suggesting that the fibers may have been derived from retained surgical swabs at the time of ovariohysterectomy. Therefore, this lesion was considered an extraskeletal osteosarcoma associated with a retained surgical swab.

Molecular epidemiological study of germline APC variant associated with hereditary gastrointestinal polyposis in dogs: current frequency in Jack Russell Terriers in Japan and breed distribution.

BACKGROUND: Cases of gastrointestinal (GI) neoplastic polyps in Jack Russell Terriers (JRTs) have increased in Japan since the late 2000s. We recently demonstrated that JRTs with GI polyps heterozygously harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT]; therefore, this is an autosomal dominant hereditary disease. We conducted a molecular epidemiological study to explore the current frequency of the APC variant in JRTs in Japan and the breed distribution of this disease. RESULTS: Peripheral blood samples from 792 JRTs were collected at 93 veterinary hospitals in Japan in 2020. Using an established polymerase chain reaction-restriction fragment length polymorphism assay, the germline APC variant was detected in 15 JRTs, with an overall frequency of 1.89%. The frequency was not significantly different for sex, age, and coat type criteria. Notably, the variant carriers had a current or previous history of GI neoplastic polyps, providing further evidence of the association of the germline APC variant with GI polyposis. Pedigree analysis of carrier dogs revealed that the germline APC variant was no longer confined to a few specific families but was widely spread among JRTs in Japan. Furthermore, some ancestors of the carriers were from Australia or New Zealand, suggesting the possible presence of carriers in countries other than Japan. Next, we retrospectively investigated the germline APC variant status of dogs with GI epithelial tumors using genomic DNA samples extracted from archived pathological specimens (28 purebred dogs of 14 breeds and four mixed-breed dog), as well as those stored in a canine genome bank (38 dogs of 18 breeds and a mixed-breed dogs). In total, 66 purebred dogs of 25 breeds, including another four JRTs, and five mixed-breed dogs were examined. While three variant carriers were found in JRTs, the germline APC variant was not detected in any of the other breeds. CONCLUSION: The current frequency of the germline APC variant was approximately 2% in JRTs in Japan and the frequency remained roughly flat during the last 15 years. In addition, hereditary GI polyposis associated with the variant was virtually specific to JRTs.

Tumour necrosis factor-related apoptosis-inducing ligand induces apoptosis in canine hemangiosarcoma cells in vitro.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an apoptosis-inducing cytokine that shows potential therapeutic value for human neoplasms, and is effective in some canine tumours; however, its potential for killing canine hemangiosarcoma (HSA) cells is unknown. Thus, we evaluated the proapoptotic effect of TRAIL in nine canine HSA cell lines. Cells (JuA1, JuB2, JuB2-1, JuB4, Re11, Re12, Re21, Ud2 and Ud6) were cultured with three recombinant human TRAILs (rhTRAILs): TRAIL-TEC derived from Escherichia coli, TRAIL-TL derived from mammalian cells and isoleucine zipper recombinant human TRAIL (izTRAIL) containing an isoleucine-zippered structure that facilitates trimerization. TRAIL-TEC did not decrease the cell viability in any of the cell lines tested, whereas the other two rhTRAILs effectively decreased the viability of all cell lines as assessed by the WST-1 assay. In canine HSA cells, izTRAIL induced apoptosis more effectively than TRAIL-TL. In JuB4, Re12, and Ud6 cells, izTRAIL increased the activation of caspase-3 and caspase-8 and caused poly (ADP-ribose) polymerase degradation. Moreover, izTRAIL treatment increased the proportion of Annexin V+/ Propidium iodide (PI)- apoptotic cells and nuclear fragmentation in izTRAIL-sensitive cells. These results show that rhTRAIL can induce apoptosis in canine HSA cells, but the sensitivity of TRAIL was different depending on the cell lines. Therefore, TRAIL could be an effective therapeutic agent against canine HSA, but the specific mechanism of resistance should be determined to clarify under what conditions this treatment would be most effective.

Hepatocellular carcinoma with intracranial metastasis in a Japanese macaque (Macaca fuscata).

BACKGROUND: A 23-year-old male Japanese macaque (Macaca fuscata) showed left ptosis, which progressed to exophthalmos. METHODS: The macaque underwent a clinical examination, CT and MRI, and was euthanized. Necropsy and histopathological examination were performed after euthanasia. RESULTS: The CT revealed and MRI confirmed an intracranial mass at the skull base with orbital extension. At necropsy, there were a large hepatic mass and an intracranial mass compressing the left temporal lobe of the brain. Histopathological and immunohistological examinations revealed that the masses were hepatocellular carcinoma (HCC) and a metastatic lesion. In both the primary and metastatic lesions, neoplastic hepatocytes were arranged mainly in a trabecular pattern. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3 and CAM5.2) and hepatocyte paraffin 1 and negative for cytokeratin 7 and 20 and vimentin. CONCLUSION: To our knowledge, this is the first case report of HCC with intracranial metastasis in a macaque.