Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease.
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.
Dog Diseases , Myeloproliferative Disorders , Skin Neoplasms , Animals , Dog Diseases/diagnosis , Dog Diseases/therapy , Dogs , Mast Cells/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Skin Neoplasms/veterinary , Subcutaneous Tissue/pathology
LIN28 is a RNA-binding protein including two highly conserved homologous, LIN28A and LIN28B. Proto-oncogenes such as LIN28A and LIN28B are generally targeted by the let-7 miRNAs in different types of human cancers. Here, we determined the expression of LIN28A in canine mammary tumor samples and the LIN28/let-7 pathway in canine mammary cell lines. In those cell lines, we identified a functional LIN28/let-7 pathway which exhibited high expression of let-7 members and low expression of its targets, including LIN28A and LIN28B. However, the mammary carcinoma tissue samples showed a frequent expression of LIN28A being expressed mainly in the epithelial cells. No association was observed between LIN28A expression and histopathological classification and grade, TNM and survival time. Our results suggested a possible role of the LIN28A protein in the development of canine mammary carcinomas due to the high frequency observed in the tumor samples (28 of 32). The in vitro experiments suggested that the LIN28/let-7 pathway is active in the tumor cells evaluated. However, more studies are necessary to elucidate the exact role of LIN28/let-7 pathway in canine mammary carcinomas.
LIN28 é uma proteína de ligação ao RNA, com duas formas homólogas altamente conservadas, LIN28A e LIN28B. Os proto-oncogenes LIN28A e LIN28B são regulados pela família de miRNAs let-7 em diferentes tipos de cânceres em humanos. No presente trabalho, o objetivo foi determinar a expressão de LIN28A em amostras de tumor mamário de cadelas e a via LIN28/let-7 em linhagens celulares mamaÌrias caninas. Nestas linhagens, atraveÌs das teÌcnicas de qPCR e RNAseq, foi identificado que a via LIN28/let-7 apresenta-se funcional, com alta expressaÌo dos membros da famiÌlia let-7 e baixa expressaÌo de seus alvos, entre eles LIN28A e LIN28B. No entanto, as amostras de tecidos de carcinomas mamaÌrios caninos demonstraram expressaÌo frequente de LIN28A, sendo observada principalmente em ceÌlulas epiteliais. NaÌo foram observadas associaçoÌes entre expressaÌo de LIN28A com classificaçaÌo e gradaçaÌo histopatoloÌgicas, TNM e tempo de sobrevida. Nossos resultados sugerem uma possível relação da proteína LIN28A no desenvolvimento de carcinomas mamários caninos devido à alta frequência observada nas amostras tumorais (28 de 32). Os experimentos in vitro sugerem que a via LIN28/let-7 é ativa nas linhagens celulares caninas avaliadas. Entretanto, estudos funcionais ainda são necessários para elucidar a função exata da via LIN28/let-7 nos carcinomas mamários caninos.
Animals , Female , Dogs , Mammary Neoplasms, Animal/genetics , RNA-Binding Proteins/analysis , MicroRNAs/analysis , Polymerase Chain Reaction
Mammary tumors are the most prevalent neoplasms in non-neutered female dogs, with genetic and epigenetic alterations contributing to canine mammary carcinogenesis. This study quantified global DNA methylation in 5-methylcytosine (5mC)-immunostained canine mammary tumor samples and established histopathological and clinical correlations. A total of 91 formalin-fixed paraffin-embedded mammary tumor samples from female dogs were retrospectively selected and subjected to immunohistochemistry using an anti-5mC mouse monoclonal antibody. We evaluated 5mC+ stained nuclei of neoplastic epithelial cells in canine mammary glands to obtain semiquantitative histoscores based on staining intensity. Survival rates were estimated based on owners' or veterinary records. Histological samples comprised 28 and 63 benign and malignant canine mammary gland tumors, respectively. Results revealed significant differences between global DNA methylation patterns when mammary samples were categorized as benign or malignant (p = 0.024), with hypomethylated patterns more prevalent in malignant tumors and those with higher relapse behavior (p = 0.011). Of note, large diameter (>5 cm) tumors revealed a lower methylation pattern (p = 0.028). Additionally, we found non-statistically significant differences when tumors were grouped by histopathological characteristics, clinical parameters, or survival. These findings propose global DNA methylation assessment as a promising tool for detecting canine mammary tumors with relapse propensity.
Tumors of the mammary glands are the most common neoplasms in dogs in our country; however, there are few Brazilian reports dedicated to clinicopathological and survival studies about this disease. This report aims the clinical and pathological study of canine mammary tumors in the Santos Metropolitan Region, an area in Sao Paulo state with an estimated canine population of 120,000 animals. Data of 14,298 dogs were collected retrospectively from the medical records of the Veterinary Medical Teaching Hospital of the Metropolitan University of Santos São Paulo Brazil. During the study period, from records of 317 females with histopathological diagnosis of neoplasia, 170 were mammary epithelial lesions distributed in 13 benign tumors, 152 malignant (89.4% of diagnosis) and 5 non-neoplasic epithelial lesions (ductal hyperplasia). The highest prevalent malignant tumor was tubular carcinoma (38.2% of diagnosis) and Grade I tumors, corresponding to 73.0% of all diagnosis. The results have shown clinical staging of canine mammary neoplasms as an important prognostic survival factor and, in a multivariate analysis, tumor diameter, tumor grade, adjuvant chemotherapy and recurrence as covariates with predictive value for survival. Moreover, the high prevalence of tubular carcinoma qualifies the canine population of Santos as a promising model for the translational study of this disease.
Os tumores das glândulas mamárias são as neoplasias mais comuns em cadelas em nosso país; no entanto, são poucos os trabalhos brasileiros dedicados ao estudo clinicopatológico e de sobrevida nesta doença. O presente trabalho teve por objetivo o estudo clínico e patológico dos tumores mamários caninos na Região Metropolitana de Santos, uma área no estado de São Paulo com uma população canina estimada em 120 mil animais. Dados de 14.298 cães foram coletados retrospectivamente dos prontuários médicos do Hospital Veterinário da Universidade Metropolitana de Santos São Paulo Brasil. Durante o período do estudo, foram atendidas 317 fêmeas com diagnóstico histopatológico de neoplasia, dos quais, 170 se referiam a lesões mamárias epiteliais distribuídas em 13 tumores benignos, 152 malignos (89,4% dos diagnósticos) e 5 lesões epiteliais não-neoplásicas (hiperplasia ductal). O tumor mais frequente foi o carcinoma tubular (38,2% dos tumores malignos) e tumores de grau I, respondendo por 73,0% do total diagnosticado. Estudos de sobrevida apontaram para o estadiamento clínico das neoplasias mamárias caninas como importante fator prognóstico, e na análise multivariada, diâmetro do tumor, grau histológico, quimioterapia adjuvante e recorrência apresentaram-se como covariáveis com valor preditivo de sobrevida. Levando-se em conta a elevada prevalência de carcinoma tubular simples na população canina de Santos, pode-se considerá-la como promissor modelo translacional para o estudo da doença.
Animals , Breast Neoplasms , Neoplasms/pathology , Survival , Drug Therapy
