Expression of platelet-derived growth factor-beta receptor and bovine papillomavirus E5 and E7 oncoproteins in equine sarcoid.

Equine sarcoids are benign fibroblastic skin tumours that are recognized throughout the world. Infection with bovine papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in disease development; however, the cellular mechanisms underlying fibroblast transformation remain poorly defined. The present study further characterizes aspects of the association with BPV in 15 equine sarcoids. BPV DNA was demonstrated in 12/15 tumours collected from different areas of Italy. Nine of these 12 tumours expressed the BPV oncoproteins E5 and E7, but these oncoproteins were not expressed by normal equine cells. The BPV E5 protein is known to bind to the platelet-derived growth factor-b receptor (PDGF-bR) and this molecule was expressed by 11 of the 12 sarcoids in which E5 was demonstrated. These findings add further weight to the theory that BPV and the PDGF-bR may have a role in the pathogenesis of this disease

Heat shock protein 90 is associated with hyperplasia and neoplastic transformation of canine prostatic epithelial cells

Heat shock protein 90 (HSP90) is a molecular chaperone that regulates critical signalling proteins of cancer development and progression. Abnormal levels of HSP90 have been observed in human prostatic carcinoma (PC), with prognostic and therapeutic implications. Since spontaneously arising canine PC is a valuable model for the human disease, the aim of this study was to evaluate the immunohistochemical expression of HSP90 in two normal canine prostates, 17 canine prostates with benign prostatic hyperplasia (BPH) and five canine prostates with PC. HSP90 was expressed in the cytoplasm of epithelial cells in all samples, with a significant increase in labelled cells in PCs. Nuclear labelling was observed occasionally in normal tissue, but was increased in BPH and PC. HSP90 immunoreactivity in preneoplastic lesions (proliferative inflammatory atrophy and prostatic intraepithelial neoplasia) was similar to that in PCs. Increased HSP90 expression in canine PCs suggests the involvement of this molecule in carcinogenesis and tumour progression, supporting HSP90 as a potential target for therapeutic intervention

Heat shock protein expression in canine malignant mammary tumours.

Background Abnormal levels of Heat Shock Proteins (HSPs) have been observed in many human neoplasms including breast cancer and it has been demonstrated that they have both prognostic and therapeutic implications. In this study, we evaluated immunohistochemical expression of HSPs in normal and neoplastic canine mammary glands and confronted these results with overall survival (OS), in order to understand the role of HSPs in carcinogenesis and to establish their potential prognostic and/or therapeutic value. Methods Immunohistochemical expression of Hsp27, Hsp72, Hsp73 and Hsp90 was evaluated in 3 normal canine mammary glands and 30 malignant mammary tumours (10 in situ carcinomas, 10 invasive carcinomas limited to local structures without identifiable invasion of blood or lymphatic vessels, 10 carcinomas with invasion of blood or lymphatic vessels and/or metastases to regional lymph nodes). A semi-quantitative method was used for the analysis of the results. Results Widespread constitutive expression of Hsp73 and Hsp90 was detected in normal tissue, Hsp72 appeared to be focally distributed and Hsp27 showed a negative to rare weak immunostaining. In mammary tumours, a significant increase in Hsp27 (P < 0.01), Hsp72 (P < 0.05) and Hsp90 (P < 0.01) expression was observed as well as a significant reduction in Hsp73 (P < 0.01) immunoreactivity compared to normal mammary gland tissue. Hsp27 demonstrated a strong positivity in infiltrating tumour cells and metaplastic squamous elements of invasive groups. High Hsp27 expression also appeared to be significantly correlated to a shorter OS (P = 0.00087). Intense immunolabelling of Hsp72 and Hsp73 was frequently detected in infiltrative or inflammatory tumour areas. Hsp90 expression was high in all tumours and, like Hsp73, it also showed an intense positivity in lymphatic emboli. Conclusion These results suggest that Hsp27, Hsp72 and Hsp90 are involved in canine mammary gland carcinogenesis. In addition, Hsp27 appears to be implicated in tumour invasiveness and its high immunodetection in invasive tumours is indicative of a poorer clinical outcome

An Update on Molecular Pathways Regulating Vasculogenic Mimicry in Human Osteosarcoma and Their Role in Canine Oncology

Canine tumors are valuable comparative models for human counterparts, especially to explore novel biomarkers and to understand pathways and processes involved in metastasis. Vasculogenic mimicry (VM) is a unique property of malignant cancer cells which promote metastasis. Thus, it represents an opportunity to investigate both the molecular mechanisms and the therapeutic targets of a crucial phenotypic malignant switch. Although this biological process has been largely investigated in different human cancer types, including osteosarcoma, it is still largely unknown in veterinary pathology, where it has been mainly explored in canine mammary tumors. The presence of VM in human osteosarcoma is associated with poor clinical outcome, reduced patient survival, and increased risk of metastasis and it shares the main pathways involved in other type of human tumors. This review illustrates the main findings concerning the VM process in human osteosarcoma, search for the related current knowledge in canine pathology and oncology, and potential involvement of multiple pathways in VM formation, in order to provide a basis for future investigations on VM in canine tumors

Xanthogranulomatous Inflammation of the Small Bowel in a Dog

A case of xanthogranulomatous inflammation of the small bowel in a 12-year-old male American Staffordshire Terrier is described. Disseminated yellow-white nodules 2 to 3 mm in diameter bulging on the serosal surface of the small bowel, as well as on mesenteric tissue, were detected. Histopathologic examination revealed a nodular collection of foamy cells, mainly involving serosal and muscular layers, associated with necrotic areas, hemorrhages, neovascularization, variable numbers of reactive spindle cells, neutrophils, lymphocytes, plasma cells, and rare multinucleated giant cells. Transmural lymphangectasia and mucosal lymphoplasmacytic inflammation were also observed. Both Oil Red O stain and ultrastructural study revealed lipid droplets in the cytoplasm of foamy cells. Lysozyme immunoreactivity was detected in single as well as in clustered foamy cells, while smooth muscle actin was positive in spindle cells and scattered foamy elements. Lymphangectasia associated with lymphoplasmacytic enteritis suggests a component of lymphatic fluid stasis in the pathogenesis of such lesions

Superficial angiomyxoma in a pregnant cow

A 3-year-old, pregnant, Alpine Brown cow showed a rapidly growing, pedunculated, skin mass located at the umbilical region, reaching 8 kg in weight over a 3-month period after its initial detection. Six days after parturition, the mass was completely surgically excised. During the follow-up period, the cow remained in good health, without signs of recurrence, and showed increased milk production. Histological examination of the mass revealed a loose proliferation of spindle-shaped or stellate cells, immersed in an abundant myxoid matrix with admixed numerous thin-walled blood vessels. Immunohistochemically, the tumour cells were positive for vimentin, α-smooth muscle actin, and desmin. Gross and histopathological features were compatible with superficial angiomyxoma, a subtype of angiomyxoma rarely described in humans, but not in the veterinary literature. The tumour did not infiltrate into the surrounding tissues, and there was no post-excision recurrence after 3 months. The possibility of hormonal dependence of the tumour during pregnancy is discussed based on such findings in some human cases

Cell proliferation patterns in canine infundibular keratinizing acanthoma and well differentiated squamous cell carcinoma of the skin

The aim of the present study was to investigate if the evaluation of cell proliferation of the well differentiated squamous cell carcinoma (WDSCC) and infundibular keratinizing acanthoma (IKA) could be useful in the differential diagnosis between these two tumours. Eighteen IKAs and ten WDSCCs were selected for this study. Two different methods were used to assess the activity of cell proliferation: MIB1 immunohistochemical detection and AgNOR proteins silver staining. The quantification of proliferative parameters was performed by means of an image analyzer and expressed as MIB1 index and AgNOR area (MNORA). Both MIB1 immunohistochemical and AgNOR histochemical patterns were different in WDSCC and IKA; moreover analysis of variance showed a significant difference for both parameters employed (MIB1 index, MNORA) between WDSCC and IKA (P<0.003 for MIB1 index; P<0.0001 for AgNOR area). The results show that canine WDSCC and IKA have a different proliferative behaviour and the assessment of cell proliferation can be considered as a useful adjunctive tool to the histopathological investigation in the differential diagnosis of these tumours

Paleopathological study of Mammuthus meridionalis of Madonna della Strada (L’Aquila)

A skeleton of a male, 50-55 years old Mammuthus meridionalis, dated to the Pleistocene and conserved at the Spanish Fort in L’Aquila (Italy), showed a broken left tusk, in association with the presence of a deep (15x20 cm) bone erosion, involving the dental alveolus and the premaxillary bone, in close proximity to the maxillary sinus and the nasal cavity. During gross examination, small samples from three representative areas of the eroded bone were obtained. Thin sections were made and the specimens were examined under plane and polarized light, using a high resolution microscope with an incorporated digital camera. Microscopical study revealed the intra vitam origin of the lesions, characterized by the presence of woven bone fibers, typical of the early phases of bone remodeling, and lamellar bone with dilated and remodeled Haversian systems. The gross and histological findings were consistent with an osteomyelitis with bone sequestration, caused by a localized blunt trauma or, more likely, resulting from an ascending, post-traumatic chronic pulpitis, due to the tusk fracture occurred during an accident or interspecies fights. The histological exam excluded the involvement of granulomatous inflammation (e.g. tuberculosis) or neoplasia. A disease process of at least several months in duration may be hypothesized, as suggested by the histologically visible bone remodeling. A long survival of the animal after tusk loss may also be supposed, since alteration of masticatory function with altered molar teeth consumption and postural changes (i.e. atlantoaxial fusion), resulting from asymmetric weight distribution, were observed. In this study, the application of (paleo)histological techniques proved to be fundamental in order to establish the nature of bone lesions detected on archeological samples, also providing a good case for studying skull trauma and shedding light on the life history of these large mammals