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.     

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.     

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.     

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.     

Classification of feline intraocular neoplasms based on morphology, histochemical staining, and immunohistochemical labeling

The objectives of this study were to evaluate morphologic, histochemical, and immunohistochemical characteristics of well-differentiated and anaplastic intraocular neoplasms of cats, and to develop a diagnostic algorithm for, and investigate the association of ruptured lenses with these neoplasms. Seventy-five feline globes with intraocular neoplasms were stained with hematoxylin and eosin and examined by light microscopy. Morphologic diagnoses included 33 intraocular sarcomas, 17 diffuse iris melanomas, 15 lymphosarcomas, three ciliary adenomas, one metastatic carcinoma, and six undifferentiated intraocular neoplasms. Sections of these globes were then stained with periodic acid Schiff (PAS), and immunohistochemical (IHC) labels for various cellular markers. Histochemical staining and IHC labeling confirmed cellular differentiation in 73/75 neoplasms but was discordant with morphologic diagnoses in 8/75. These included four neoplasms morphologically diagnosed as lymphosarcomas but which expressed differentiation antigens consistent with melanoma (n = 3) or ciliary adenocarcinoma (n = 1), and four tumors morphologically diagnosed as intraocular sarcomas that expressed differentiation antigens for melanoma (n = 2), metastatic carcinoma (n = 1), or remained undifferentiated (n = 1). Immunohistochemical labeling suggested a diagnosis in 5/6 morphologically undifferentiated neoplasms including one intraocular sarcoma, two diffuse iridal melanomas, and two ciliary adenocarcinomas. Based upon morphologic, histochemical, and IHC characterization, ruptured lens capsules were detected in 28/30 intraocular sarcomas, 3/24 diffuse iris melanomas and 1/11 lymphosarcomas, but not in ciliary epithelial neoplasms, metastatic carcinomas, or undifferentiated intraocular neoplasms. An algorithm is provided that facilitates stain and IHC label selection for differentiating anaplastic intraocular feline neoplasms.     

Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled prospective study

In this study, we evaluated the treatment of feline eosinophilic plaques and lip ulcers with amoxicillin trihydrate–potassium clavulanate (Clavamox^®; Pfizer Animal Health). Nineteen cats with clinical and cytological findings consistent with eosinophilic plaques and/or lip ulcers were enrolled. Lesions were photographed and their areas measured in square centimetres before and after 21 days of therapy with either flavoured amoxicillin‐clavulanate suspension or flavoured placebo suspension. Sixteen cats completed the study, with nine plaque lesions (four treatment and five placebo) and eight lip ulcer lesions (four treatment and four placebo) included in the analysis. All lesions were shown to have infection, with bacterial phagocytosis present on cytological examination. Coagulase‐positive staphylococci were the most commonly isolated bacteria. The amoxicillin‐clavulanate‐treated eosinophilic plaque group had a statistically significant 96.2% reduction in mean lesion size (?7.60 cm², P = 0.0078) and an 80% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), whereas the placebo group did not. The amoxicillin‐clavulanate‐treated lip ulcer group had a 42.6% decrease in mean lesion size (?0.25 cm², P = 0.4125) and the placebo group a 36.6% increase (+0.49 cm², P = 0.1575), although neither change was statistically significant. The amoxicillin‐clavulanate‐treated lip ulcer group had a statistically significant 65.0% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), while no significant reduction was observed in the placebo group. A suspension of amoxicillin trihydrate–potassium clavulanate is an effective monotherapy for the treatment of feline eosinophilic plaques.     

Histologic and immunohistochemical characterization of lens capsular plaques in dogs with cataracts

OBJECTIVE: To determine histologic and immunohistochemical characteristics of the multifocal adherent plaques that commonly develop on the internal surfaces of the anterior and posterior lens capsules in dogs with cataracts. SAMPLE POPULATION: 31 anterior and 4 posterior capsular specimens collected during lens extraction surgery in dogs with cataracts. PROCEDURE: Specimens were evaluated, using light and transmission electron microscopy. Immunohistochemical techniques were used to localize cytokeratin, vimentin, alpha-smooth muscle-specific actin, fibronectin, tenascin, and transforming growth factor-beta (TGF-beta) within plaques. RESULTS: Histologically, plaques comprised elongated spindle-shaped cells that formed a placoid mass. Cells were embedded in an extracellular matrix containing collagen fibrils, often with duplicated or split basement membranes. Immunohistochemically, normal lens epithelial cells and cells within plaques stained for vimentin. Most cells and some areas of the extracellular matrix within plaques stained for TGF-beta and alpha-smooth muscle-specific actin. Fibronectin and tenascin were also detected in the extracellular matrix. CONCLUSIONS AND CLINICAL RELEVANCE: Canine lens capsular plaques are histologically and immunohistochemically similar to posterior capsule opacification and subcapsular cataracts in humans, which suggests that the canine condition, like the human conditions, is associated with fibrous metaplasia of lens epithelial cells. Transforming growth factor-beta may play a role in the genesis of capsular plaques. Because severity of plaques was correlated with stage of cataract development, earlier surgical removal of cataracts may be useful to avoid complications associated with plaque formation.     

A retrospective study of the clinical, histological, and immunohistochemical manifestations of 5 dogs originally diagnosed histologically as necrotizing scleritis

Purpose To describe the clinical, histological, and immunohistochemical manifestations of canine necrotizing scleritis. Methods A retrospective examination of the clinical records and samples of ocular tissues from five dogs with a histological diagnosis ‘necrotizing scleritis’ was completed. Archived, formalin‐fixed, paraffin‐embedded samples and two control globes were stained with hematoxylin and eosin, Gram, periodic acid–Schiff (PAS) and Masson trichrome stains, and they were immunohistochemically labeled for CD3, CD18, and CD20. Results Of the five cases reviewed, only two could be confirmed as idiopathic necrotizing scleritis. The other three cases were retrospectively diagnosed as unilateral focal, non‐necrotizing scleritis, one as episcleritis and the third was scleritis secondary to a proptosed globe based on our retrospective clinical, histological, and immunohistochemical evaluations. In these two cases, idiopathic necrotizing scleritis manifested as a bilateral, progressive, inflammatory disease of the sclera and cornea that induces significant uveitis. Light microscopic examination confirmed collagen degeneration and granulomatous inflammation. There was no evidence for an infectious etiology based on Gram’s and PAS stainings. Immunohistochemical labeling revealed a predominance of B cells in idiopathic, bilateral necrotizing scleritis. Tinctorial staining abnormalities with Masson’s trichrome stain were present in scleral collagen of the two cases with idiopathic necrotizing scleritis as well as a case of secondary traumatic scleritis. Conclusions Based on a limited number of cases, idiopathic canine necrotizing scleritis shares similar histopathological features with non‐necrotizing scleritis and episcleritis; however, necrotizing scleritis is B‐cell‐dominated and bilateral, and significant collagen alterations manifest with Masson’s trichrome stain.     

Strain-specific viral distribution and neuropathology of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIV(PPR) (PPR, relatively apathogenic but associated with neurologic manifestations), FIV(C36) (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3' C36 genomic elements contribute to viral replication characteristics, and (ii) 5' PPR genomic elements contribute to CNS manifestations. This study illustrates the potential for FIV to provide valuable information about neuroAIDS pathogenesis related to genotype and viral kinetics, as well as to identify strains useful to evaluation of therapeutic intervention.     

Clinical aspects of feline immunodeficiency and feline leukemia virus infection

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries.     

Expression of viral proteins in feline leukemia virus-associated enteritis

Fourteen cases of feline leukemia virus (FeLV)-associated enteritis were immunohistologically examined for the expression of FeLV proteins gp70, p27, and p15E in the jejunum, mesenteric lymph nodes, spleen, and bone marrow. Results were compared with those of FeLV-infected cats without intestinal alterations. Other viral infections and specific bacterial, fungal, and parasitic infections were excluded by standard microbiologic methods, histopathology, immunohistology, and in situ hybridization. In FeLV-associated enteritis, FeLV gp70 and p15E were strongly expressed in intestinal crypt epithelial cells. In contrast, FeLV-positive cats without intestinal alterations showed only faint staining for gp70 and p15E and comparatively strong p27 expression in these cells. Findings suggest a direct relation between FeLV infection and alterations in intestinal crypt epithelial cells that may be attributed to the envelope proteins gp70 and p15E and/or their precursor protein. Distinct similarities to the intestinal changes in the experimentally induced FeLV-feline AIDS syndrome are obvious, suggesting that naturally occurring feline AIDS variants may be responsible for FeLV-associated enteritis.     

Pathologic, immunohistochemical, and electron microscopic findings in naturally occurring virulent systemic feline calicivirus infection in cats

Infection with feline calicivirus (FCV) is a common cause of upper respiratory and oral disease in cats. FCV infection is rarely fatal, however, virulent, systemic strains of FCV (VS-FCV) that cause alopecia, cutaneous ulcers, subcutaneous edema, and high mortality in affected cats have recently been described. Seven cats with natural VS-FCV infection all had subcutaneous edema and ulceration of the oral cavity, with variable ulceration of the pinnae, pawpads, nares, and skin. Other lesions that were present in some affected cats included bronchointerstitial pneumonia, and pancreatic, hepatic, and splenic necrosis. Viral antigen was present within endothelial and epithelial cells in affected tissues as determined by immunohistochemical staining with a monoclonal antibody to FCV. Mature intranuclear and intracytoplasmic virions in necrotic epithelial cells were identified by transmission electron microscopy. VS-FCV infection causes epithelial cell cytolysis and systemic vascular compromise in susceptible cats, leading to cutaneous ulceration, severe edema, and high mortality.     

An immunohistochemical and polymerase chain reaction evaluation of feline plasmacytic pododermatitis

Sections of 14 skin biopsies of cats with plasmacytic pododermatitis and a clinical follow-up of 12-36 months were stained with a polyclonal anti-Mycobacterium bovis (Bacille Calmette-Guerin = BCG) antibody cross-reactive to a broad spectrum of fungi and bacteria. All sections were negative for organisms within the actual footpad tissue with the anti-BCG antibody stains. Polymerase chain reaction (PCR) assays that amplify the DNA of Bartonella spp., Ehrlichia spp., Anaplasma phagocytophilum, Chlamydophila felis, Mycoplasma spp., Toxoplasma gondii, and feline herpesvirus 1 (FHV-1) were applied to tissue digests. DNA of those pathogens assessed was not amplified from tissue.     

Coordinate expression of cytokeratins 7 and 20 in feline and canine carcinomas.

Forty-seven feline and 60 canine epithelial tumors were studied to test the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase staining technique. Previously, the distribution of both cytokeratins was examined in normal tissues from 4 cats and 4 dogs. The pattern of distribution of CK 7 in normal tissues was similar, with minor differences, to that described in humans, whereas the reactivity pattern of CK 20 in cats and dogs was wider than that in humans. The subset of tumors strongly expressing CK 7 and CK 20 included pancreatic adenocarcinomas (100%), transitional cell carcinomas (75%), and endometrial carcinomas (67%) in the cat. None of the canine tumors had this immunophenotype. Feline (50%) and canine (56%) mammary gland carcinomas and canine cholangiocarcinomas (67%) were the only tumors presenting the CK 7 +/CK 20- immunophenotype, whereas the CK 7-/CK 20+ immunophenotype included thyroid carcinomas (100%), intestinal adenocarcinomas (60%), bronchioloalveolar carcinomas (50%), and renal carcinomas (50%) in the cat and intestinal adenocarcinomas (56%), gastric adenocarcinomas (50%), and ovarian carcinomas (50%) in the dog. The CK 7-/CK 20- immunophenotype included the rest of the analyzed tumors. The immunohistochemical evaluation of coordinate expression of both CK 7 and CK 20 in feline and canine carcinomas using monoclonal antibodies provides important information that can help to discriminate among carcinomas from different primary sites and could be particularly helpful in the determination of the primary site of origin of carcinomas presenting as metastatic disease.