Canine squamous cell carcinoma: Electrochemotherapy association with surgery and correlation with overall survival.

Squamous cell carcinoma (SCC) is an important malignancy in dogs, due to its incidence and clinical presentation, which can be of locally aggressive single or multiple lesions with a metastatic potential. The objective of this investigation was to evaluate SCC response to treatment, anatomopathological and immunohistochemical characteristics, disease-free interval and overall survival time. 54 dogs with histopathologically diagnosed SCC were included in this study. Their mean age was 9.16 years with a range of 1-14 years. Of the 54 animals in the study, 34 (65.4%) had white skin and white fur coats. There was a significant correlation between fur coat colour and the development of tumours in areas of sun exposure (p = .001). Animals with tumours in areas of the body exposed to the sun had longer overall survival time than animals with tumours in areas not associated with sun exposure (p = .001). Surgery combined with electrochemotherapy (ECT) yielded a survival rate 32% higher than using a surgical approach alone (HR = 0.32, p = .038, IC = 0.11-0.94). ECT, with or without surgery, had an objective response rate of 90.9%. Local lymph node and/or distant site metastasis at diagnosis, or at some point during follow-up, occurred in 34.6% (18/52) of animals. Animals with tumours in sun exposed locations had more aggressive histopathological characteristics but had longer overall survival time. This is probably due to individualised therapeutic treatment with both surgery and ECT.

Inclusion of fibroblasts and collagen fibrils in the cytologic grading of canine cutaneous mast cell tumors.

BACKGROUND: Fibroblasts and/or collagen fibrils have not been included in previous cytologic grading schemes of canine mast cell tumors (MCTs), and their association with biological behavior is broadly debated. OBJECTIVES: This study aimed to evaluate the cytologic findings of canine MCT, with emphasis on the microenvironment, and propose a novel cytologic grading system correlated with mortality and histologic grade. MATERIAL AND METHODS: Cytology smears of canine cutaneous MCTs were retrospectively reviewed and compared with their histopathologic counterparts using Cohen´s Kappa test. One-year survival rates were also compared with the cytologic and histopathologic variables using Pearson´s correlation test. RESULTS: From 92 first-occurrence canine cutaneous MCTs, the five features most associated with mortality were selected for a new grading system. The five features were cytoplasmic granulation, fibroblast and/or collagen fibril concentrations, and the presence of mitotic figures, multinucleation, and karyomegaly. Among concordant histopathologic and cytologic cases (ie, the same grades using both systems), mortality rates were 2.6% (1/38) for low-grade and 71.4% (10/14) for high-grade cases (P < 0.001, chi-square). For false-negative and false-positive results, mortality rates were 33% (1/3) and 45% (5/11), respectively (P = 0.707). CONCLUSIONS: Unlike the Camus cytologic grading system, the present amendment excluded binucleation and included fibroblasts and/ or collagen fibrils, which in higher concentrations were associated with increased survival and a low histopathologic grade. Cytologic grading with the inclusion of fibroblast and collagen fibril concentrations correlated with survival, as did the Camus cytologic and Kiupel histopathologic grades; however, further studies are needed to confirm the prognostic value of this novel cytologic grading scheme.

Diagnosis, Prognosis and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors.

Mast cell tumors (MCTs) are hematopoietic neoplasms composed of mast cells. It is highly common in dogs and is extremely important in the veterinary oncology field. It represents the third most common tumor subtype, and is the most common malignant skin tumor in dogs, corresponding to 11% of skin cancer cases. The objective of this critical review was to present the report of the 2nd Consensus meeting on the Diagnosis, Prognosis, and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors, which was organized by the Brazilian Association of Veterinary Oncology (ABROVET) in August 2021. The most recent information on cutaneous and subcutaneous mast cell tumors in dogs is presented and discussed.

Erratum to "Mixed tumors of the canine mammary glands: Evaluation of prognostic factors, treatment, and overall survival" [7C (June 2019) 100039].

[This corrects the article DOI: 10.1016/j.vas.2018.09.003.].

Coenzyme Q10 Cardioprotective Effects Against Doxorubicin-Induced Cardiotoxicity in Wistar Rat.

In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart's oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity.

Mixed tumors of the canine mammary glands: Evaluation of prognostic factors, treatment, and overall survival.

Mixed tumors are the most frequent mammary gland neoplasms in bitches; however, studies that thoroughly describe their clinicopathological data, treatment approaches, and the survival of bitches with mixed tumors are scarce. This study evaluated the epidemiological and clinicopathological data, prognostic factors, and therapeutic approaches for bitches with mixed tumors. In all, 162 benign mixed tumors, 682 carcinomas in mixed tumors, and 60 carcinosarcomas were included. Regarding tumor size, T3 lesions were predominantly associated with carcinosarcomas, while T1 and T2 lesions occurred more frequently in benign mixed tumors and in carcinomas in mixed tumors. Based on clinical staging, most bitches with benign mixed tumors presented with stage I tumors; 92% of bitches with carcinomas in mixed tumors presented with stage I-III tumors, while 8% presented with stage IV-V tumors; and 70% of bitches with carcinosarcomas presented with stage I-III tumors, while 30% presented with stage IV-V tumors. Surgery was curative for bitches with benign mixed tumors and for those with stage I-III carcinomas in mixed tumors. Combination therapy in bitches with carcinomas in mixed tumors (IV-V) and carcinosarcomas resulted in a higher overall survival compared with bitches who underwent surgery only. Carcinosarcomas presented higher relapse rates and distant metastases than carcinomas in mixed tumors did.

Adjuvant Thalidomide and Metronomic Chemotherapy for the Treatment of Canine Malignant Mammary Gland Neoplasms.

BACKGROUND/AIM: The aim of the present study was to evaluate a multimodal approach for the treatment of canine malignant mammary gland neoplasms, including surgery, chemotherapy, thalidomide, and metronomic chemotherapy (MC). MATERIALS AND METHODS: Fifty-eight female dogs were submitted to four different treatments: surgery; surgery with chemotherapy; surgery with chemotherapy and thalidomide; and surgery with chemotherapy and metronomic chemotherapy and overall survival was evaluated. RESULTS: No statistical difference was found in the proliferative index and microvessel density of primary neoplasms and distant metastases following thalidomide treatment. Diffuse intense inflammatory infiltrate was predominant in primary tumors and diffuse moderate inflammatory infiltrate in metastatic lesions. No statistically significant difference was observed in median survival time (MST) between treatment groups when including all clinical stages (p=0.3177). However, animals diagnosed with distant metastasis treated with surgery and chemotherapy associated with thalidomide or MC presented longer MST when compared to animals treated only with surgery or surgery and chemotherapy (p<0.0001). CONCLUSION: The proposed multimodal therapy protocols including antiangiogenic and immunomodulatory therapies demonstrated a clinical benefit for patients in advanced clinical stages.

Consensus for the diagnosis, prognosis and treatment of feline mammary tumors / Consenso para o diagnóstico, prognóstico e tratamento de tumores mamários em felinos

Mammary neoplasms are described as the third most common type of feline tumor, after haematopoietic and skin tumors, and present a challenge for clinicians because the prognosis for feline mammary tumors ranges from guarded to poor. Thus, it is necessary to define new therapeutic approaches and establish more in-depth knowledge about this disease in felines. The main aspects of the diagnosis, prognosis and treatment of feline mammary neoplasia were discussed, aiming to standardize the criteria and to serve as a guide for pathologists and veterinary clinicians.(AU)

As neoplasias mamárias são descritas como o terceiro tipo mais frequente de tumor em felinos (após as neoplasias hematopoiéticas e cutâneas) e apresentam um desafio para os clínicos devido ao prognóstico, que varia de reservado a ruim. Assim, é necessário conhecer melhor essa doença em felinos e definir novas abordagens terapêuticas. Discutiu-se os principais aspectos de diagnóstico, prognóstico e tratamento da neoplasia mamária felina, com o objetivo de padronizar os critérios e servir de guia para patologistas e clínicos veterinários.(AU)

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high-risk canine mast cell tumours to tyrosine kinase inhibitors.

The aim of the present prospective-retrospective study was to evaluate the response of high-risk canine mast cell tumours (MCTs) to tyrosine kinase inhibitors (TKIs) and to correlate this with prognostic factors. A total of 24 dogs presented with macroscopic cutaneous MCTs at disease stage II or III, and therefore, at high-risk of associated mortality, were included in the study and treated with masitinib (n=20) or toceranib (n=4). A total of 12/24 dogs achieved an objective response and the overall survival (OS) for all subjects was 113 days. Dogs responding to treatment had a significant increase in OS compared to non-responders (146.5 days vs. 47 days, P=0.02). Internal tandem duplications in exon 11 of the c-kit gene were identified in 6/24 cases. Ki67, KIT immunolabelling and c-kit mutation did not provide information regarding prognosis or prediction of response to TKIs in this population. Initial response to TKIs appears to be the most reliable prognostic factor for survival duration.

Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, rP = -0.610), history of tumor recurrence ( P < .0001, rP = -0.550), Patnaik ( P < .0001, rP = -0.380) and Kiupel grades ( P < .0001, rP = -0.500), predominant organization of neoplastic cells ( P < .0001, rP = -0.452), mitotic count ( P < .0001, rP = -0.325), Ki-67 labeling index ( P < .0001, rP = -0.414), KITr pattern ( P = .02, rP = 0.207), and c-KIT mutational status ( P < .0001, rP = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

Electrochemotherapy treatment of oral extramedullary plasmacytoma of the tongue: a retrospective study of three dogs / Eletroquimioterapia no tratamento de plasmocitoma extramedular oral na língua: estudo retrospectivo de três cães

ABSTRACT: Extramedullary plasmacytomas (EPs) are responsible for 2.5% of neoplasms in dogs. They are solitary, smooth, elevated, pink or red nodules, of 1 to 2cm in diameter. Cutaneous and oral extramedullary plasmacytomas in dogs are usually benign tumors, treated with local therapies. Prognosis is generally good. Recurrence and metastatic rates are low. Electrochemotherapy is a local treatment that combines chemotherapy and electroporation and shows objective responses of 70% to 94% with few local and systemic side effects. This scientific communication has the objective to report treatment of three canine patients with oral extramedullary plasmacytoma. Nodules were located on the tongue and patients were submitted to one or two electrochemotherapy sessions, which preserved the tongue without mutilation and cured the patients.

RESUMO: Plasmocitomas extramedulares (PE) são responsáveis por 2,5% das neoplasias em cães. São nódulos solitários, lisos, elevados, rosados ou avermelhados, de 1 a 2cm de diâmetro. O plasmocitoma extramedular cutâneo e oral em cães é um tumor tipicamente benigno tratado com terapias locais. O prognóstico geralmente é bom. As taxas de recorrência e metástase são baixas. A eletroquimioterapia é um tratamento local que combina quimioterapia e eletroporação e mostra respostas objetivas entre 70 a 94% com poucos efeitos colaterais locais e sistêmicos. Esta comunicação científica teve como objetivo relatar o tratamento de três pacientes caninos com plasmocitoma extramedular oral com lesões localizadas na língua submetidos a uma ou duas sessões de eletroquimioterapia, o que permitiu a manutenção da língua sem mutilação e proporcionou a cura dos pacientes.

Cyclooxygenase-2 expression in epithelial neoplasms and its relevance as a targeted therapy in dogs / Expressão de ciclooxigenase-2 em neoplasias epiteliais e sua relevância como terapia alvo em cães

ABSTRACT: Targeted therapy of neoplasms is an emergent approach in human and veterinary medicine. Cyclooxygenase (COX) is a class of catalytic enzymes related to the formation of inflammatory mediators. COX-2 is expressed constitutively in a few body tissues, but it may be induced in specific pathophysiologic conditions, such as cancer. COX-2 expression in neoplams may be considered a potential predictive factor, due to the possible association of selective COX-2 inhibitors in adjuvant treatments. This scientific communication has the objective to report COX-2 expression in seven neoplasms of dogs and the usage of adjuvant treatment with COX-2 selective inhibitors as an effective and feasible option in cancer treatment.

RESUMO: O tratamento direcionado das neoplasias é uma abordagem emergente tanto na medicina humana, quanto na veterinária. A cicloxigenase (COX) é uma classe de enzimas catalíticas relacionada à formação de mediadores inflamatórios. A COX-2é expressa de forma constitutiva em poucos tecidos, mas pode ser induzida em condições patofisiológicas específicas, como os processos neoplásicos. A expressão da COX-2 em neoplasias pode ser considerada um fator preditivo em potencial, tendo em vista a possibilidade de associação de inibidores seletivos para COX-2 em tratamentos adjuvantes. Esta comunicação científica teve como objetivo relatar a expressão de COX-2 em neoplasias de sete cães e o tratamento adjuvante com inibidores seletivos para COX-2 como uma opção efetiva e viável no tratamento do câncer.

Evaluation of prognostic factors and survival rates in malignant feline mammary gland neoplasms.

OBJECTIVES: The aim of the study was to investigate prognostic factors in feline mammary gland neoplasms, correlating them with overall survival (OS). METHODS: Fifty-six primary malignant mammary gland neoplasms and 16 metastatic lymph nodes from 37 female cats were analyzed. Clinical staging, histologic type and grade, and immunohistochemistry for Ki-67, progesterone and estrogen receptor, human epidermal growth factor receptor type 2 (HER-2), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were evaluated. Follow-up was performed in order to correlate prognostic factors with OS. RESULTS: Lymph node metastasis was found in 35% of cases. Clinical stage III, tubulopapillary carcinomas and histologic grade II cases prevailed in the study. Most neoplasms were positive for hormonal receptors, negative for HER-2 overexpression and presented VEGF overexpression. Immunoreactivity for Ki-67 (P = 0.046) and COX-2 (P = 0.007) was higher in metastases than in primary tumors. COX-2 (P = 0.089), HER-2 (P = 0.012) and histologic grade (P = 0.080) were correlated with OS. CONCLUSIONS AND RELEVANCE: The data suggest that inhibition of ovarian hormones and COX-2 may represent a therapeutic option for malignant feline mammary gland neoplasms. When evaluating disease progression, COX-2 scores and Ki-67 index should be analyzed in primary tumors and metastases. Histologic grade, HER-2 status and COX-2 scores were found to have a direct influence on OS. Prognostic factors allow for a better understanding of disease outcome in a condition that is characterized by a poor prognosis. The present work highlights the need for further studies on endocrine therapy and COX-2 inhibitors, which could influence OS.

Prognostic significance of tissue and serum HER2 and MUC1 in canine mammary cancer.

The aim of our study was to compare serum levels and protein tissue of human epidermal growth factor receptor-2 proto-oncogene (HER2) and mucin 1 (MUC1) using an antigen-capture enzyme-linked immunosorbent assay and immunohistochemistry (IHC) in canine mammary carcinomas and investigate how the 2 markers correlate with dogs with metastasis and without metastasis to a regional lymph node. Forty-eight female dogs were selected, including 14 with non-metastatic cancer, 14 with lymph node metastasis, and 20 healthy animals. Serum samples were collected from all the animals and tissues from 28 dogs with malignant mammary tumor with or without metastasis for evaluated HER2 and MUC1 expression. Tissue sample were evaluated for MUC1 and HER2 immunoexpression by IHC. The results showed measurable serum levels of MUC1 and HER2 in all groups. While serum MUC1 levels were significantly higher in animals with metastasis than the other 2 groups, no increase was observed in HER2 serum levels. The MUC1 IHC results showed that only membrane immunostaining was significantly different between the groups. Statistically, there was an association between immunostaining and the serum HER2 levels. Our results indicate that serum concentrations of HER2 and the IHC staining pattern for HER2 in primary tumor do not correlate with the presence of regional metastasis. However, increased concentrations of MUC1 in the serum of dogs with mammary cancer are associated with the presence of metastasis to regional lymph nodes. A membrane pattern of IHC staining for MUC1 in the primary tumor suggests that metastases to regional lymph node are present.

Surgical stress and postoperative complications related to regional and radical mastectomy in dogs.

BACKGROUND: Surgery is the treatment of choice for regional control of mammary neoplasms in female dogs. Various surgical techniques may be used, as long as mammary gland anatomy, lymphatic drainage, and known prognostic factors are respected. The purpose of this study was to compare surgical stress-including duration of surgery, nociception and hematological changes-and postoperative complications in dogs undergoing regional and unilateral radical mastectomy. Eighteen dogs were selected for each technique. Postoperative pain (nociception), hematological changes, and postoperative complications were compared between the two groups. RESULTS: The group treated with radical mastectomy had a longer surgical duration, showed more intense physiological changes, achieved higher scores on nociception scales, and experienced more postoperative complications. CONCLUSION: Compared to regional mastectomy, radical mastectomy was associated with longer surgical duration, greater nociceptive stimulus, greater surgical stress, and higher incidence of postoperative complications in dogs. Although evaluation of long-term results was not a goal of this study, it is suggested that postoperative recovery and patient quality of life should be considered when choosing a surgical approach for treating mammary tumors in dogs.

Use of surgery and carboplatin in feline malignant mammary gland neoplasms with advanced clinical staging.

BACKGROUND/AIM: Feline mammary carcinomas (FMCs) are characterized by poor prognosis and little progress has been made in extending patient survival. The aim of the study was to compare overall survival periods of FMCs submitted to different treatment protocols, including surgery and adjuvant chemotherapy. MATERIALS AND METHODS: Analysis of conventional surgical excision alone or in association with adjuvant chemotherapy with carboplatin in sixteen cats diagnosed with stage III and grade II or III FMCs was performed. RESULTS: Patients treated with surgery and chemotherapy presented a longer overall survival (OS) than those treated only with surgery, however, no statistical difference was observed when comparing both treatments (p=0.883). CONCLUSION: Therapeutic benefit of carboplatin remains invalidated for FMCs and further investigation regarding adjuvant therapies are warranted. Surgery remains as the gold treatment in FMCs.

Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs / Caracterização histomorfológica e imuno-histoquímica de 172 neoplasias cutâneas de células redondas em cães

This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin) on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes) are required for definitive diagnosis of round cell tumours in dogs.

Este trabalho descreve o uso de um painel de anticorpos (CD117, CD3, CD79a, CD45, citoqueratina, vimentina e e-caderina em tecidos formalizados e parafinizados para o diagnóstico de neoplasias de células redondas em cães. Os tumores foram diagnosticados usando-se a histopatologia e a marcação imuno-histoquímica. Foram incluídos 107 mastocitomas, 31 histiocitomas cutâneos, 2 sarcomas histiocíticos localizados, 21 linfomas cutâneos, 3 plasmocitomas, 1 tumor venéreo transmissível e 7 tumores de células redondas não classificados. O diagnóstico histológico foi modificado em 39,5% do total de 172 neoplasias. A marcação do anticorpo CD45 e E-caderina foi variável e, nesse sentido, o diagnóstico final de histiocitoma cutâneo e sarcoma histiocítico localizado foi baseado na histologia em associação com os resultados negativos para CD3, CD79a, CD117 e citoqueratina. A origem celular dos tumores de células redondas não classificados foi definida em todos os casos. Linfoma cutâneo de célula B e plasmocitoma foram positivos para CD79a e foram distinguidos entre si pelas características morfológicas. Marcação positiva para vimentina e negativa para CD3, CD79a, CD117 e citoqueratina favoreceram o diagnóstico dos tumores venereos transmissíveis. Assim, o diagnóstico final dos tumores de células redondas foram baseados na interpretação dos resultados da imuno-histoquímica em conjunto com a avaliação das características morfológicas observadas na histologia. Finalmente, mais estudos em relação à padronização de marcadores específicos para tecidos parafinizados (especialmente para histiócitos) são necessários para o diagnóstico definitivo das neoplasias de células redondas em cães.

Fatores prognósticos e preditivos dos tumores caninos definidos com auxílio da imuno-histoquímica / Prognostic and predictive factors of canine tumours defined with immunohistochemistry's assistance

A imuno-histoquímica pode ser aplicada na oncologia veterinária para a definição do imunofenótipo neoplásico, com possibilidades ilimitadas de utilização. A técnica baseia-se na identificação de antígenos "in situ", que podem apresentar valor prognóstico e terapêutico. A expressão de receptores de estrógeno e progesterona está diretamente relacionada ao melhor prognóstico para os neoplasmas mamários, enquanto a super-expressão do receptor KIT (CD117), proteínas Ki-67 (MIB-1), VEGF, CD31 e COX-2 podem ser associados à progressão tumoral para vários tipos histológicos. Essa associação possui valor preditivo em potencial, tendo em vista a possibilidade da utilização de bloqueadores específicos. Esta revisão tem como objetivo apresentar as possibilidades da utilização da imuno-histoquímica nos tumores de cães, visando à definição mais precisa do prognóstico e a indicação de tratamentos específicos para cada paciente.

Immunohistochemistry can be applied in veterinary oncology to define the immunophenotype of neoplastic cells with unlimited possibilities of application. The technique is based on the identification of antigens "in situ", which may have prognostic and therapeutic value. Expression of estrogen and progesterone is directly related to better prognosis for breast cancer, while over-expression of receptor KIT (CD117) proteins Ki-67 (MIB-1), COX-2, VEGF and CD31 can be associated with tumor progression for several histological types. This association has a potential predictive value, due to the possibility of using specific blockers. This revision aims at presenting the possibilities of immunohistochemical's application in tumors of dogs, searching for a more precise definition of the prognosis and indication of specific treatments for each patient.

Canine malignant mammary gland neoplasms with advanced clinical staging treated with carboplatin and cyclooxygenase inhibitors.

Surgery remains the treatment of choice for female dogs with mammary gland tumors. Chemotherapy is not commonly used as an adjuvant therapy. Cyclooxygenase 2 (COX-2) has been related to angiogenesis development in tumors, disease progression and worse prognosis. The aim of this prospective study was to compare overall survival periods of female dogs diagnosed with advanced mammary tumors submitted to different treatment protocols, including surgery, chemotherapy and cyclooxygenase inhibitors. Twenty-nine female dogs were evaluated and treated with four different protocols. The overall survival of patients with low COX-2 scores was longer when compared to patients with high COX-2 scores. Different proposed adjuvant treatments associated with surgery led to a statistically significant longer overall survival when compared to surgical treatment alone. Canine patients presenting malignant mammary gland neoplasms with advanced clinical staging should be submitted to complementary therapeutic medication based on clinical staging and immunophenotypical characteristics of the disease.

Evaluation of adverse effects in tamoxifen exposed healthy female dogs.

BACKGROUND: Mammary tumors are among the most frequent neoplasms in female dogs, but the strategies employed in animal treatment are limited. In human medicine, hormone manipulation is used in cancer therapy. Tamoxifen citrate is a selective inhibitor of oestrogen receptors and exerts a potent anti-oestrogen effect on the mammary gland. The aim of this study was to evaluate the adverse effects when exposing healthy female dogs to tamoxifen. METHODS: Tamoxifen was administered for 120 days at a dose of 0.5 or 0.8 mg/kg/day to either intact or spayed female dogs. The effects were assessed through clinical examination, haematology, serum biochemistry, ophthalmology and bone marrow aspirate examination. Ovariohysterectomy was performed and the uterus examined by histopathology. RESULTS: Vulva oedema and purulent vaginal discharge developed with 10 days of tamoxifen exposure in all groups. Pyometra was diagnosed after around 90 days of exposure in intact females with frequencies increasing during the following 30 days of exposure. Up to 50% of dogs within the groups developed retinitis but none of the dogs had signs of reduced visual acuity. The prevalence of retinitis in each group was similar after 120 days of exposure. Haematological, biochemical and bone marrow changes were not observed. Due to the high risk of developing pyometra after prolonged exposure to tamoxifen, only spayed animals should be given this medication. CONCLUSIONS: A dose of 0.8 mg tamoxifen/kg body weight/day is recommended when treating tamoxifen-responsive canine mammary tumors. Due to the high risk of developing pyometra, ovariohysterectomy is recommended.