Erythropoietin receptor expression in canine mammary tumor: an immunohistochemical study

Erythropoietin (EPO) is a cytokine primarily involved in the regulation of the erythropoiesis. Recently, it has been demonstrated that EPO and its receptor (EPOR) are expressed in several neoplastic cell lines and solid tumors. Furthermore, in vitro and in vivo studies have shown that EPO could promote human breast carcinoma growth by means of the binding with its receptor, although a clear function for EPO in this setting has not been yet established. While the human medical literature has been accumulating strong evidence on EPO's role in oncogenesis, to date, there are no veterinary reports focusing on such an issue. The aim of the present study was to investigate the immunohistochemical expression of EPOR in canine mammary gland dysplastic and neoplastic lesions. Our results show a weak to moderate EPOR expression in dysplastic glands, being immunoreactivity enhanced as the lesion shows an increasing malignant pattern. On the basis of these findings, this study describes, for the first time, the evidence for EPOR expression in canine mammary gland tumor and suggests a feasible EPO's role for canine mammary tumor progression.     

An immunohistochemical study of canine disseminated aspergillosis

An immunohistochemical study of 25 lesions from 7 dogs with disseminated aspergillosis (Aspergillus terreus) is presented. All had multiple fungal granulomas in many viscera, with centres of necrotic tissue and hyphal elements surrounded by a mixed infiltrate of predominantly mononuclear cells. Within these lesions, hyphae coated with immunoglobulin (IgG, IgM, IgA) and complement (C3, C4) were identified, together with peri-lesional mononuclear cells that reacted with antisera directed towards either IgG, IgM, IgA or a T lymphocyte marker (MUII). A conspicuous feature was the prominent hyphal fluorescence seen with IgA and C3 antisera. The IgA reagent also marked large numbers of mononuclear cells both around lesions and scattered throughout interstitial tissue, suggesting an abnormality of IgA production or regulation as a factor predisposing to this condition.     

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.     

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.     

Immune-mediated canine and feline keratitis.

Although the normal cornea is devoid of vasculature and lymphatics, there are still several immune-mediated corneal conditions that can occur in dogs and cats. An overview of corneal immunology is presented. Diseases of dogs, including chronic superficial keratitis, superficial punctate keratitis, and canine adenovirus endotheliitis, as well as feline diseases, including eosinophilic keratitis and herpesvirus-related conditions, are discussed.     

Perspectives on canine and feline hepatozoonosis

Two species of Hepatozoon are currently known to infect dogs and cause distinct diseases. Hepatozoon canis prevalent in Africa, Asia, southern Europe, South America and recently shown to be present also in the USA causes infection mainly of hemolymphoid organs, whereas Hepatozoon americanum prevalent in the southeastern USA causes myositis and severe lameness. H. americanum is transmitted by ingestion of the Gulf Coast tick Amblyomma maculatum and also by predation on infected prey. H. canis is transmitted by Rhipicephalus sanguineus, in South America also by Amblyomma ovale, and has also been shown to be transmitted transplacentally. Hepatozoonosis of domestic cats has been described mostly from the same areas where canine infection is present and the exact identity of the species which infect cats, their pathogenicity and vectors have not been elucidated. The diagnosis of hepatozoonosis is made by observation of gamonts in blood smears, histopathology, PCR or serology. The main treatment for H. canis is with imidocarb dipropionate whereas H. americanum infection is treated with an initial combination of trimethoprim-sulfadiazine, pyrimethamine and clindamycin followed by maintenance with decoquinate. Treatment for both diseases has not been reported to facilitate complete parasite elimination and new effective drugs are needed for the management of these infections. Prevention of hepatozoonosis should be based on avoidance of oral ingestion of infected tick vectors and infected prey.     

Ex vivo viability of canine and feline sarcomas: a pilot study

Assay-based chemotherapeutic protocols are common in human gynecologic oncology, most notably for patients with ovarian or breast cancer. The current study examines ex vivo incubation conditions necessary for the assessment of sarcomatous tumor response to potential chemotherapeutic drugs. Slices of sarcomatous tumors were incubated in one of two culture media. Viability indices were measured and compared across time and between media. Neither medium was sufficient to support the growth of sarcomatous tumor tissue slices based on the indices studied. It is likely that sarcomatous tumors require a different approach for ex vivo assessment than their epithelial counterparts. Our long-term goal is to incubate tumor slices with chemotherapeutic agents to predict the in vivo tumor response based on the maintenance or loss of slice viability within this system.     

Clinical, histological and immunohistochemical study of feline viral plaques and bowenoid in situ carcinomas

Feline viral plaques (FVP) induced by papillomavirus (PV) are often hyperpigmented and flat warts. The fact that up to 47% of bowenoid in situ carcinomas (BISC), which also usually occur in the form of hyperpigmented plaques, are positive for PV antigen in immunochemistry suggests that BISC could evolve from FVP. The relationship between the presence of PV antigens and the clinical and histological features of 26 cases of feline dermatoses (clinically described as pigmented plaques and with histological diagnosis of FVP and/or BISC) was therefore determined. The cases were classified into one of the three following groups: FVP, FVP + BISC or BISC. Immunohistological detection of papillomavirus group-specific antigen was performed using a polyclonal rabbit antibovine papillomavirus antiserum. Of the seven cases in the FVP group, six were deemed positive by immunohistology as were all 10 cats in the FVP + BISC group. On the other hand, only one of the nine BISC cats was positive. The presence of both FVP and BISC lesions in some cats and the high detection rate of PV antigens in the FVP and FVP + BISC groups suggest that both conditions might have the same viral cause and that some BISC may evolve from FVP. The low rate of viral antigen detection in the BISC group indicates another cause or a loss of viral replication during the cancerogenesis.     

Topical treatment of canine and feline pyoderma

Abstract This paper is a review of commonly used topical antibacterial medications: benzoyl peroxide, chlorhexidine, povidone iodine, ethyl lactate, triclosan, mupirocin, neomycin, polymyxin B, bacitracin and fusidic acid. Included is a review of the pharmacokinetics, modes of action, adverse effects and clinical uses in veterinary dermatology. General recommendations for topical antibacterial therapy are presented. Résumé— Cet article est une revue des topiques antibactériens les plus couramment utilisés: peroxyde de benzoyle, chlorhexidine, povidone iodée, lactate d'éthyle, triclosan, mupirocine, néomycine, polymyxine B, bacitracine et acide fucidique. Il inclut notamment une revue des pharmacocinétiques, des modes d'action, des effets secondaires et des indications thérapeutiques de ces produits en dermatologie vétérinaire. Les indications générales du traitement topique antibactérien sont présentées. [Guaguere, E. Topical treatment of canine and feline pyoderma. (Traitement topique des pyodermites canines et félines). Veterinary Dermatology 1996; 7 : 145–151.] Resumen Este articulo es una revisión de los productos tópicos antibacterianos más frecuentemente utilizados: peróxido de benzoilo, clorhexidina, povidona yodada, etillactato, triclosan, mupirocina, neomicina, polimixina B, bacitracina y ácido fusidico. Se incluye una revisión de la farmacocinética, mecanismos de acción, efectos colaterales y sus usos clínicos en dermatologia veterinaria. Se presentan recomendaciones generales para la terapia antibacteriana tópica. [Guaguere, E. Topical treatment of canine and feline pyoderma. (Tratamiento topico de la pioderma canina y felina). Veterinary Dermatology 1996; 7 : 145–151.] Zusammenfassung— Diese Veröffentlichung besteht in einer Übersicht von häufig verwendeten topischen antibakteriellen Arzneimitteln: Benzoylperoxid, Chlorhexidin, Povidon-Jod, Ethyllaktat, Triklosan, Mupirocin, Neomycin, Polymyxin B, Bacitracin und Fusidinsäure. Mit eingeschlossen ist eine Übersicht über Pharmakokinetik, Wirkungsweise, Nebenwirkungen und klinische Anwendung in der Veterinärdermatologie. Allgemeine Empfehlungen für die lokale antibakterielle Therapie werden dargestellt. [Guaguere, E. Topical treatment of canine and feline pyoderma (Lokale Behandlung von kaninen und felinen Pyodermien). Veterinary Dermatology 1996; 7 : 145–151.]     

Microbiology of the canine and feline eye

Knowledge of the microbiology of the canine and feline eye in normal and pathologic states is an important aspect of the clinician's assessment of external ocular disease. Gram-positive bacteria predominate in surveys of microbial flora in normal and diseased eyes. These same organisms are routinely isolated from skin and the upper respiratory tract. Injury to the eye may result in proliferation and potential pathogenicity of normal ocular flora. A variety of bacterial, fungal, viral, and other microbial isolates affect the diagnosis and treatment of external ocular disease.     

Current research in canine and feline pheromones.

Pheromonotherapy seems to be a new therapeutic approach allowing practitioners to tackle the treatment of behavioral disorders in a natural, specific, and safe way. Although the efficacy of pheromones has been assessed in some specific behavioral problems, it seems that their range of action could cover the wide field of reduction of stress. Therefore, the use of pheromones should not be reduced to treatment of behavioral disorders (potentially associated with psychotropes or a behavioral modification program) but should be included in a strategy of improving the welfare of pets in veterinary structures (during examination and hospitalization) and in breeding networks (separation from the mother and transport). Moreover, further studies may allow the veterinary practitioner to use pheromone analogues in the field of diagnostics to determine the behavioral status of a pet (e.g., anxious or not, dominant or not). Pheromonotherapy is at its beginning, and the use of pheromones in various fields of medicine is heartening.     

Apoptosis in feline panleukopenia and canine parvovirus enteritis

Tissue samples of cats and dogs with panleukopenia and parvovirus enteritis, respectively, were examined for the presence of viral antigen-positive cells and apoptotic cells by immunohistochemistry and by TUNEL assay (Terminal Transferase-Mediated dUTP Nick End Labelling). Compared to control animals, infected cats and dogs generally had more TUNEL-positive cells. Cell types positive for parvovirus antigen, for example digestive tract epithelial and mesenchymal cells, and lymphocytes and macrophages in lymphoid tissues were also positive for TUNEL signals. Occasionally, TUNEL signal and viral antigen were present in the same tissue areas, suggesting a direct viral trigger of apoptosis. More frequently, however, there was no complete overlap of antigen and TUNEL-positive areas. The results of this study indicate that apoptotic cell death contributes significantly to the widespread tissue damage of parvovirus infection in cats and dogs.     

Comparison of steroid receptor expression in normal, dysplastic, and neoplastic canine and feline mammary tissues

Steroid receptor expression was assessed by immunohistochemistry in neoplastic, hyperplastic/dysplastic, and normal mammary tissue samples removed from 68 queens and 47 bitches, using monoclonal antibodies against human oestrogen-alpha (ER) and progesterone receptors (PR). Mammary lesions were classified according to World Health Organization (WHO) criteria, and all animals with invasive carcinomas were clinically followed for 2 years. Stromal and/or lymphatic invasion and histological grading were also recorded. In both species, ER expression was significantly higher in healthy tissues, hyperplastic/dysplastic lesions, and benign tumours than in carcinomas. The loss of ER expression was more marked in feline than in canine carcinomas. In queens, PR expression increased in dysplastic lesions and "in situ" carcinomas and decreased in invasive carcinomas, even if parts of these tumours were still PR-positive. In bitches no significant variation in PR expression was observed between normal tissue, dysplasias, and benign neoplasms, but was significantly lower in carcinomas. In both species ER and PR expression in invasive carcinomas did not correlate either with histological parameters or overall survival time. This study demonstrates several differences in steroid hormone dependency between the two species. The percentage of PR-positive feline carcinomas suggests a possible role of progesterone in promoting early tumour cell growth in queens. The low percentage of ER-positive invasive carcinomas further demonstrated the aggressive phenotype and behaviour of feline mammary tumours.     

Tumour necrosis factor in the canine endometrium: an immunohistochemical study

Tumour necrosis factor (TNF), a pleiotropic cytokine that regulates cell growth and differentiation as well as the synthesis of other cytokines, has been identified in the uterus of several species describing a cyclic pattern, eventually under ovarian steroid regulation. Information is yet limited on the presence of TNF protein in the canine endometrium during the oestrous cycle and early pregnancy. This study depicts the temporal immunolocalization of TNF in the bitch endometrium along the oestrous cycle and changes associated with the early steps of embryo invasion. TNF immunolabelling was found in both the stromal fibroblasts and epithelial components of the canine endometrium in all stages studied. Stromal immunostaining was more intense than that of the epithelia, in all the stages of the oestrous cycle. In addition, a tendency for a decrease in the surface epithelium intensity score was found in early dioestrus. A positive glandular content was only observed in anoestrus and proestrus stages. In early pregnancy (days 13-16), TNF immunolabelling was detected at the embryo-maternal surface, in the syncytium cords and the trophoblast, as well in the endometrial stroma and the basal endometrial glands, but not in the lacunar epithelium. The overall TNF immunoreactivity was higher in early pregnancy samples in comparison with those of the early dioestrus and dioestrus stages, suggesting it plays a role during implantation.     

Pathology of the canine and feline uterine tube

Lesions of the uterine tube were described in 37 dogs and nine cats. Of the 52 lesions noted, 18 were developmental abnormalities; four paramesonephric remnants, and 14 mesonephric remnants. Uterine tube cysts were seen in 16 animals, and seven animals had salpingitis. One dog had hyperplastic changes of the infundibular mucosa, and one cat and one dog demonstrated adenomyosis. There were three primary benign uterine tube neoplasms, one adenocarcinoma, two metastatic neoplasms in the uterine tube, and two bursal lipomas, all in dogs. With the exception of neoplasia of the uterine tube, most lesions were unlikely to affect the reproductive performance of these animals and/or were incidental or secondary to disorders elsewhere in the reproductive tract.