Loss of retinoblastoma protein, but not p53, is associated with the presence of papillomaviral DNA in feline viral plaques, Bowenoid in situ carcinomas, and squamous cell carcinomas

Although papillomaviral (PV) DNA is frequently present in feline cutaneous squamous cell carcinomas (SCCs), a causative association cannot be proven. Oncogenic human PVs cause neoplastic transformation by inhibiting retinoblastoma (pRb) and p53 activity. Therefore, absence of pRb and p53 immunostaining, along with increased p16 immunostaining, indicates a PV cause in some human SCCs. If PVs cause cutaneous feline SCCs, it was hypothesized that a similar immunohistochemistry profile, along with PV DNA, would be detectable. This was investigated using 5 feline viral plaques, 10 Bowenoid in situ carcinomas, 19 SCCs from ultraviolet-exposed (UV-exposed) skin, and 11 SCCs from UV-protected skin. Papillomaviral DNA was amplified by polymerase chain reaction from 30 of 45 lesions. Reduced pRb immunostaining was present in 26 of 45; increased p16 immunostaining was in 30; and p53 immunostaining was in 19. Both reduced pRb immunostaining and increased p16 immunostaining were more frequent in lesions containing PV DNA. In contrast, no association was observed between p53 immunostaining and the presence of PV DNA. SCCs from UV-protected skin more frequently contained PV DNA, reduced pRb, and increased p16 than UV-exposed SCCs. UV exposure was not associated with p53 immunostaining within the SCCs. These results suggest that feline PVs alter cell regulation by degrading pRb. Unlike oncogenic human PVs, there was no evidence that feline PVs degrade p53. These results provide further evidence that PVs may cause feline cutaneous SCCs, especially those in UV-protected skin, and they suggest a possible mechanism of this oncogenic action.     

Multiparametric survival analysis of histological stage and proliferative activity in feline mammary carcinomas

Mammary tumours are among the most frequent malignant neoplasms in the cat and determination of prognosis on histological grounds alone can be unsatisfactory because it does not always correspond to the clinical behaviour of the neoplastic disease. The aim of this two-year post-mastectomy survival study is to relate the histological stage or invasiveness (the most commonly used histological parameter to grade malignancy) to several parameters assessing the proliferative activity-mitotic index, MIB1 index, and AgNOR index. Invasiveness was graded as local and vascular invasion whilst values of the parameters expressing proliferative activity, all quantified by image analysis, have been classified into low and high proliferative activity groups according to their median values, (0.719 for mitotic index, 12.11 for MIB1 index, and 3.19 for AgNOR index). For each group, mean survival (months+/-SD) was calculated. Histological stage (local invasion 21.83+/-7.83 months, blood vessels and/or lymphatics invasion 13.38+/-8.99,P<0.01), mitotic index (low 22.43+/-88.78, high 12.37+/-7.49,P<0.001), and AgNOR index (low 21.86+/-10.68, high 13.82+/-7.11,P<0.05) revealed a significant association with survival in univariate analysis and had an independent prognostic value in multiparametric survival test (P<0.001).     

Cell proliferation in feline normal, hyperplastic and neoplastic mammary tissue--an immunohistochemical study

The expression of a proliferation cell marker in neoplastic and non-neoplastic mammary tissue in 31 cats was assessed by immunohistochemistry in formalin-fixed paraffin-embedded samples using a monoclonal antibody against nuclear antigen Ki-67 (MIB-1). The results revealed that cell proliferation was more intense in hyperplastic than in normal mammary tissue. Carcinomas exhibited a higher MIB-1 index than benign tumours. There was also a positive correlation between proliferative activity and the histological grade of carcinomas. Fibroadenomatous change, which is considered to be hyperplastic and associated with favourable biological behaviour, exhibited high proliferative activity involving both epithelial and mesenchymal components. MIB-1 detected in formalin-fixed material with pre-treatment with antigen retrieval solution appeared to be a reliable marker of proliferation in feline mammary tumours, but further studies are needed to investigate the value of this proliferation marker in predicting clinical outcome and/or as a prognostic factor in feline mammary lesions.     

Clinical, pathological and immunohistochemical study of feline mammary fibroepithelial hyperplasia following a single injection of depot medroxyprogesterone acetate

Feline mammary fibroepithelial hyperplasia (FMFH) following a single injection of depot medroxyprogesterone acetate (MPA) was observed in eight intact young queens. The repository compound is marketed as a veterinary product by a local pharmaceutical company with an indication for contraception in cats. The drug was administered according to the recommended doses and injection frequencies. Serum hormone assays performed immediately before neutering and 3 weeks after neutering detected persistently high levels of progesterone suggesting that depot MPA was still exerting its influence. No corpora lutea were found in those cases ruling out ovaries as the main site of progesterone. Immunohistochemistry performed on the hyperplastic mammary glands detected progesterone receptors in the nuclei of ductal cells, and growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the cytoplasm of ductal epithelium. Overdosing should be considered here as the animals received at least 10 mg/kg of depot MPA in a single injection. Progestin-induced local synthesis of GH and IGF-I in mammary epithelial cells is suggested as one of the pathogenic mechanisms involved in the development of FMFH.     

An immunohistochemical study of cyclooxygenase-2 expression in various feline neoplasms

Cyclooxygenase (COX) enzymes catalyze the synthesis of prostaglandins and exist as two isoforms, COX-1 and COX-2. COX-2 is a potent inducible mediator of inflammation. COX-2 is also upregulated in several human tumors and in canine squamous cell, renal cell, and transitional cell carcinomas, prostatic adenocarcinoma, and intestinal neoplasia. The purpose of this study was to determine whether COX-2 is expressed in various feline tumors. Results of this study may help determine whether COX-2 is a potential target for therapeutic and preventive strategies in cats. Immunohistochemical studies were performed on paraffin-embedded tissues using the amplified streptavidin-biotin-horseradish peroxidase system. COX-2 was found in 7 of 19 (37%) feline transitional cell carcinomas and in 2 of 21 (9%) feline oral squamous cell carcinomas. No COX-2 immunoreactivity was detected in cutaneous squamous cell carcinomas (6), adenocarcinomas (nine mammary, eight pulmonary, seven intestinal), lymphomas (six nasal, six intestinal), or 10 vaccine-associated sarcomas. The widespread absence of COX-2 expression in most feline neoplasms might suggest that COX-2 inhibitors would have a low potential as anticancer agents.     

Oestrogen and progesterone receptors in feline fibroadenomatous change: an immunohistochemical study

The distribution of oestrogen and progesterone receptors was analysed in 18 cases of feline fibroadenomatous change (FFAC) using commercially available specific monoclonal antibodies and the Avidin-biotin peroxidase complex technique on formalin-fixed, paraffin-embedded tissue. In all cases of FFAC, progesterone receptors were detected either in epithelial cells (mostly suprabasal) or in epithelial and stromal cells. Oestrogen receptors were detected in approximately half of these cases, in suprabasal or luminal epithelial cells exclusively. Myoepithelial cells lacked both oestrogen and progesterone receptors. The techniques used have identified the specific cellular distribution of steroid hormones receptors in this hormone-dependent lesion of the feline mammary gland. The results confirm those of previous biochemical analyses with respect to progesterone receptors and add new data concerning the possible involvement of oestrogen receptors and stromal fibroblasts in the hormonal control and development of the lesion.     

Preliminary immunohistochemical study of natriuretic peptide receptor localization in canine and feline heart

We examined the immunohistochemical distributions of natriuretic peptide receptor (NPR)-A, -B and -C that bind with natriuretic peptide hormones A, B and C in four healthy crossbreed young canine and feline cardiac tissues using specific antibodies against human antigens. Cross-immunoreactivities between antigens and antibodies were confirmed using western blot analysis. NPR-A and -C were expressed more strongly in dogs than cats. In both species, these expressions were stronger in the atria than the ventricles, with stronger expression in the left ventricles than the right. NPR-B was largely very weekly or undetected. In canine and feline cardiac tissues, the expressional distribution of NPR-A, -B, and -C closely matched with that of atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide as the ligands for corresponding receptors.     

Overexpression of HER-2 in feline invasive mammary carcinomas: an immunohistochemical survey and evaluation of its prognostic potential

The role of c-erbB-2 protooncogene status in feline invasive mammary carcinomas (FMCs) was assessed through the HER-2 receptor immunohistochemical expression. The HER-2 overexpression was then correlated with some relevant histologic parameters and with the clinical course of the disease during a 2-year follow-up. Forty-seven FMCs from surgically treated queens were considered. Tumors were classified according to the WHO criteria and stromal or lymphatic invasion (or both) and histologic grading were recorded. The immunohistochemical staining was performed on paraffin sections and a well-defined scoring system based upon numbers of HER-2 receptors expressed on the cell surface was applied according to standard guidelines. Overall survival (OS) distributions were generated with the Kaplan-Meier method. HER-2 overexpression was detected in 28 of the 47 carcinomas (59.6%). This parameter was demonstrated to be significantly correlated with the shorter OS (P = 0.02). However, the HER-2 overexpression did not show significant correlation with histologic type, tumor grading, or presence of lymphatic invasion. Furthermore, the HER-2 overexpression appeared with a higher percentage in FMCs than what is reported in canine or human mammary carcinomas. The significant correlation with a shorter OS suggests a possible role of HER-2 as an additional marker of malignancy in FMCs and as a reliable prognostic indicator. As in the human oncology practice, the identification of the FMCs that overexpress HER-2 may also promote new therapeutic strategies.     

Development of multiple pigmented viral plaques and squamous cell carcinomas in a dog infected by a novel papillomavirus

Canine viral plaques are uncommon skin lesions that are induced by papillomaviruses (PVs). Plaques are usually of little clinical significance in dogs, although they have been reported rarely to progress to squamous cell carcinoma (SCC). Here is described a 7‐year‐old mixed‐breed dog that developed numerous darkly pigmented plaques up to 8 cm in diameter. Multiple ulcerated nodular masses were visible within plaques on the ventrum and axilla. The dog showed no clinical evidence of immunodeficiency and appeared otherwise healthy. Over the next 2 years, five surgeries were performed to remove 23 ulcerated masses that ranged in size from 2 to 5 cm in diameter. Five masses were submitted for histology, and all were SCCs. Each was surrounded by epidermis that contained histological features consistent with those described in canine plaques. Suggestive of a PV aetiology, massive numbers of large keratohyaline granules were present throughout the thickened epidermis. Additionally, koilocytes were focally present, and one sample contained a band of keratinocytes within the superficial epidermis that contained pale cytoplasm and marginated chromatin. From two samples, DNA sequences from a previously unreported PV were amplified, and immunohistochemistry confirmed the presence of PV antigen in both. The PV DNA sequences were most similar to those of canine PVs previously associated with plaque formation. The plaques observed in this case were unusual owing to their rapid growth, large size and frequent malignant transformation. It is unknown whether this unusual behaviour was due to the specific PV detected in this case or to host factors within the dog.     

A survey of feline viral rhinotracheitis and feline picornavirus infection in Britain

A survey of healthy and respiratory-diseased cats, post-mortem kitten specimens and serum samples, showed the widespread occurrence of feline rhinotracheitis virus infection (FVR) and feline picornavirus infection (FPI) in Britain. Both virus groups were on occasions isolated from clinically healthy cats but they were more frequently associated with upper respiratory disease. No colony outbreak of respiratory disease was investigated without either FVR or FPI being incriminated. Clinical differentiation of FVR and FPI was imposible with certainty although FVR infection was typically more severe. Pathologically, FVR could be distinguished particularly in the early stages by the presence of specific intranuclear inclusions in mucosal and submucosal gland cells of the respiratory tract and by a generally more severe mucosal destruction. FPI was typified by a mild disorganization of mucosae and mononuclear cell infiltrations. Serological investigations demonstrated that, in colonies particularly, high titres of antibody against both FVR virus and a spectrum of feline picornaviruses were attained in adult cats, a reflection of the endemic nature of these viruses. Bacteria played a secondary role in both FVR and FPI, and there was no evidence for chlamydial agents being important in the aetiology of feline respiratory disease in Britain. Résumé. Une étude de chats sains et atteints de maladies des voies respiratoires, de spécimens d'autopsie de chatons et d‘échantillons de sérum montre que les rhinotrachéites félines avec infection d'origine virale (RFV) et les infections ftlines de “picornavirus” (IFP) sont très répandues en Grande-Bretagne. A différentes occasions, les deux groupes de virus, provenant de chats sains du point de vue clinique, ont été isolés mais ces virus étaient le plus souvent lies aux maladies respiratoires d'origine otorhinolaryngologique. Toutes les recherches sur les maladies respiratoires se declarant par colonies indiquaient la présence soit de RFV ou de I'IFP. La dif-férenciation clinique certaine de RFV et d'IFP fut impossible bien que l'infection RFV fût plus grave come prévu. Pathologiquement, il fut possible de distinguer le RFV, surtout dans les premiers stades, par la présence d'inclusions intranucléaires spécifiques dans les cellules des glandes muqueuses et submuqueuses des voies respiratoires et par une destruction muqueuse généralement plus grave. L'IFP était caracterisée par une légère désorganisation des membranes muqueuses et des infiltrations de cellules mononucléaires. Des recherches sérologiques ont montré, surtout pour les colonies, qu'on rencontre des titres élevés d'anticorps contre le virus RFV ainsi qu'un spectre de “piconavirus” felins chez des chats adultes, ce qui réflète la nature endémique de ces virus. Les bactéries n'ont joué qu'un rôle secondaire, à la fois dans les RFV et les IFP et il n'y eut pas d'indices indiquant l'importance des agents “Chlamydiaux” dans l‘étiologie des maladies respiratoires félines en Grande-Bretagne. Zusammenfassung. Ein zusammenfassender Bericht über geusunde Katzen und solche mit Erkrankungen der Atmungsorgane, Sektionsproben junger Katzen und Serumproben zeigte das verbreitete Auftreten der Rhinotracheitis-Virus infektion der Katzen (FVR) und der Picornavirusinfektion der Katzen (FPI) in Grossbritannien. Beide Virusgmppen wurden gelegentlich aus klinisch gesunden Katzen isoliert, waren aber häufiger mit Erkrankungen der oberen Atemwege verbunden. Es wurde kein massiertes Auftreten von Erkrankungen der Atmungswege untersucht, ohne dass entweder FVR oder FPI als Ursache anzusehen waren. Die klinische Differenzierung von FVR und FPI war nicht mit Sicherheit möglich, obwohl die FVR-Infektion typisch schwerer war. Pathologisch konnte FVR besonders in den Frühstadien durch die Anwesenheit spezifischer intranuklearer Einschlüsse in mucösen und submucösen Drüsenzellen des Respirationstraktes und durch eine allgemein schwerere Schleimhautzer-störung unterschieden werden. FPI war durch eine schwache Disorganisation mucöser und mononuklearer Zellinfiltrationen charakterisiert. Serologische Untersuchungen zeigten, dass besonders in Kolonien hohe Antikörperkonzentrationen gegen FVR-Virus und ein Spektrum von Picornaviren der Katze bei erwachsenen Katzen erreicht wurden, was auf den endemischen Charakter dieser Viren hinweist. Bakterien spielten bei FVR und FPI eine sekundäre Rolle, und es liess kein Anzeichen darauf schliessen, dass chlamydiale Agentien für die Ätiologie der Erkrankungen der Atmungsorgane von Katzen in Grossbritannien eine Rolle spielten.     

Haemangiopericytoma: histological spectrum, immunohistochemical characterization and prognosis

Canine haemangiopericytoma (CHP) is a vascular neoplasm thought to be derived from pericytes. The histological pattern and immunohistochemical profile were studied in 31 CHPs. Twenty-three subjects were followed for 2 years to evaluate the correlation among tumour location, histotype, immunostaining and outcome of the disease. Of the 31 CHPs examined, 20 exhibited a perivascular whorled pattern, 8 were storiform and 3 were epithelioid. All tumours were positive for vimentin and negative for cytokeratin, factor VIII-related antigen, glial fibrillary acidic protein and S-100 protein. Seventeen CHPs were positive for actin and nine co-expressed desmin. Six CHPs were also positive for CD34 antigen. The panel of immunohistochemical markers used confirmed the vascular lineage of CHP and aided in the exclusion of other mesenchymal tumours. Of the 23 dogs submitted to follow-up, 6 had recurrence or metastases of the primary tumour. The epithelioid pattern or a noncutaneous location were associated with a poorer prognosis.     

Quantification of EGFR family in canine mammary ductal carcinomas in situ: implications on the histological graduation

Veterinary Research Communications - The epithelial growth factor receptors are transmembrane proteins with an important role in the neoplastic progression of tumors, and in this context, DCIS is...     

猫病毒性鼻气管炎的诊断与防治

猫病毒性鼻气管炎病毒,又名猫疱疹病毒1型（Feline Herpesvirus type1,FHV-1）,属于疱疹病毒科中的α-疱疹病毒,可引起猫及其他猫科动物的眼病及呼吸道疾病,发病率可达100％,成年猫死亡率很低,但幼猫的死亡率可达50％。本病在世界范围内广泛流行,我国己多次发现临床可疑病例。猫感染FHV-1后,虽然有抗体产生,但病毒可潜伏到三叉神经节,     

Interaction of an intranasal combined feline viral rhinotracheitis, feline calicivirus vaccine and the FVR carrier state

Eight cats were vaccinated intranasally with a combined feline calicivirus/feline viral rhinotracheitis (FVR) virus commercial vaccine. Following intranasal challenge with a field strain of FVR virus and subsequent treatment with corticosteroid, no virus was recovered from any of the eight cats, while FVR virus was recovered following corticosteroid treatment from two of four unvaccinated and challenged controls. No evidence was found for the development of an FVR virus carrier state with the intranasal vaccine virus.     

Pathologic and immunohistochemical findings in a feline aortic body tumor

The presence of a heart-base tumor was diagnosed by ultrasound imaging in a 10-year-old, female, domestic shorthaired cat presenting with dyspnea and pleural effusion because of the presence of a modified transudate. Hematology and clinical chemistry were unremarkable. The owner elected euthanasia. At necropsy, a locally extensive, firm, multilobulated nodule surrounded the pulmonary vein. The tumor was composed of lobules of large polygonal cells separated by a fine fibrovascular stroma. Tumor cells infiltrated the myocardium, and neoplastic emboli were present, but no metastases were macroscopically detectable. Tumor cells were immunohistochemically positive for chromogranin A, for synaptophysin and, faintly, for neuron-specific enolase and negative for vimentin, cytokeratin, alpha smooth muscle actin, glial fibrillary acidic protein, thyreoglobulin, and calcitonin. Based on histologic and immunohistochemical findings, the diagnosis of chemodectoma was made.     

Epidemiological,pathological and immunohistochemical aspects of 125 cases of feline lymphoma in Southern Brazil

A retrospective study compiling cases of feline lymphoma diagnosed during 12 years (2004‐2016) in Southern Brazil was performed. A total of 125 cases of lymphoma diagnosed in cats were reviewed, and information including age, breed, sex and tumour topography were collected. FeLV and FIV immunohistochemical tests were performed, as well as immunophenotyping of lymphomas. The alimentary form represented the most common presentation (42/125), followed by mediastinal lymphoma (35/125). Out of 125 cases, 79 presented positive retroviral immunostaining in tumour tissue (52 FeLV alone, 14 FIV alone and 13 presented FIV and FeLV co‐infections), 66/125 of the cases were of T‐cell origin and 59/125 of the cases were of B‐cell origin. The median age of cats with T‐cell lymphoma was 120 months (10‐240 months), and 60 months (6‐204 months) for cats with B‐cell lymphoma. The most frequent alimentary tumour presentation was the enteropathy‐associated T‐cell lymphoma (type 1), and the major type of mediastinal tumour observed was diffuse large B‐cell lymphoma. Considering only mediastinal and alimentary lymphomas (n = 77), the prevalence of mediastinal lymphoma in FeLV‐positive cats was 2.21 times higher than the prevalence of this type of tumour in FeLV‐negative cats (P = .036). Mediastinal lymphoma was more frequently observed in younger cats, and the prevalence of mediastinal tumours in these animals was 3.06 times higher than the prevalence of this tumour form in old cats (P = .0125). The present study indicates that retroviral infections still play an important role in the development of feline lymphomas in southern Brazil.     

Immunophenotypic and histological characterisation of 109 cases of feline lymphosarcoma

OBJECTIVE: To determine and analyse the immunophenotype and histological appearance of naturally occurring cases of lymphosarcoma in Australian cats. DESIGN: A prospective multi-institutional study of naturally occurring feline lymphosarcoma. METHODS: One hundred and eighteen cats were referred for diagnosis and/or management of suspected lymphosarcoma. Tissue samples for histopathological analysis and immunophenotyping were collected as biopsies or at necropsy from 109 cases. Histological classification of the neoplasms followed the Working Formulation Classification System. Four multi-species cross-reactive antibodies were used to classify tumours as having a B or T cell phenotype. RESULTS: Seventy-six (70%) cases were B cell tumours and 28 (26%) were T cell tumours. The remaining 5 (4%) specimens failed to stain with the four antibodies. Histologically, 11 (10%) cases were classified as low-grade, 72 (66%) were medium-grade and 26 (24%) were high-grade tumours. There were no significant associations between age and either histological grade or immunophenotype. Mediastinal and leukaemic cases were significantly more likely to be T cell tumours (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: In contrast to previously documented studies in the cat, the majority of cases of lymphosarcoma were of B cell phenotype and intermediate histological grade. Based on our data, the histological phenotype of lymphosarcoma is unlikely to predict immunotype, nor are cases of certain immunotypes likely to be of specific histological subtype. Considered in relation to previous reports, the findings suggest that epidemiological factors operating in these cats to produce lymphosarcoma may be different to those operating in North American and UK cat populations.     

In vitro antiviral efficacy of ribavirin against feline calicivirus, feline viral rhinotracheitis virus, and canine parainfluenza virus.

Ribavirin had marked in vitro activity against feline calcivirus, strain 255, and canine parainfluenza virus, but showed only slight antiviral effect on feline viral rhinotracheitis virus. Antiviral activity was manifested by partial to complete suppression of viral cytopathic effect and of viral replication, depending on concentration of ribavirin in the culture medium and dosage of viral inoculum. Concentrations of ribavirin as small as 3.2 microgram/ml and 1.0 microgram/ml showed some activity against feline calcivirus and canine parainfluenza virus, respectively.