RESUMO
Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protein expression) with overall survival in HSA-affected patients. Fifty-three formalin-fixed and paraffin-embedded canine splenic HSA samples, previously diagnosed by histopathological examination, were used in this study. Claudin-5, PSMA, and Ki67 protein expression levels were evaluated by immunohistochemistry, and gene expression was evaluated by quantitative polymerase chain reaction. Claudin-5 protein overexpression was observed in patients with metastasis (p = 0.0078) and with stage III tumors compared to those with stage I and II tumors (p = 0.0451). In patients treated with surgery alone, low PSMA gene and protein expression (p = 0.05 and p = 0.0355, respectively) were associated with longer survival time. Longer survival time was observed in patients with a low Ki67 index (p = 0.0488). Our results indicate that Claudin-5 protein expression is associated with metastatic status, and PSMA gene and protein expression, and Ki67 index are associated with survival time.
RESUMO
BACKGROUND: The antibody Ki-67 is a reliable and easy tool to accurately assess the growth fraction of neoplasms in humans and animals, and it has been used to predict the clinical outcome. Therefore, the aim of the present study was to investigate the immunohistochemical expression pattern of Ki-67 in normal and neoplastic perianal glands of dogs to evaluate the possible use of this proliferation marker as an ancillary method of perianal tumor diagnosis. We studied 42 cases of perianal gland neoplasms including adenomas (n = 15), epitheliomas (n = 15), and carcinomas (n = 12). As controls, 13 tissue samples from normal perianal glands were used. A Ki-67 index was established by a computer-assisted image analysis and compared with manual counting. RESULTS: Out of the 42 cases of perianal gland neoplasms, 34 were from males and eight from females. Recurrence was reported in 14 cases, being higher (8/12) in carcinomas. Immunostaining for Ki-67 revealed that the carcinomas showed a higher proliferation rate (9.87%) compared to groups of epitheliomas (2.66%) and adenomas (0.36%). For adenomas and epitheliomas of the perianal glands the computer-assisted counting and the manual counting gave similar results; however, only the computer-assisted image analysis was efficient to predict the perianal gland carcinoma recurrence. CONCLUSION: Since there were significant differences in the number of Ki-67-positive nuclei, this marker proved to be effective in helping the classification of perianal gland neoplasms and to refine the diagnosis criteria, especially in those samples with high variation in morphology/area. Also, higher Ki-67 index is related to recurrence in cases of perianal gland carcinomas. Further, the computer-assisted image analysis proved to be a fast and reliable method to assess the Ki-67 index in perianal gland neoplasms.
Assuntos
Neoplasias das Glândulas Anais/diagnóstico , Doenças do Cão/diagnóstico , Antígeno Ki-67/análise , Adenoma/diagnóstico , Adenoma/imunologia , Adenoma/metabolismo , Adenoma/veterinária , Neoplasias das Glândulas Anais/imunologia , Neoplasias das Glândulas Anais/metabolismo , Animais , Biomarcadores/análise , Carcinoma/diagnóstico , Carcinoma/imunologia , Carcinoma/metabolismo , Carcinoma/veterinária , Proliferação de Células , Doenças do Cão/imunologia , Doenças do Cão/metabolismo , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Processamento de Imagem Assistida por Computador , Antígeno Ki-67/biossíntese , Masculino , Glândulas Perianais/química , Glândulas Perianais/metabolismo , PrognósticoRESUMO
A apoptose e a proliferação celular possuem uma participação importante na tumorigênese, determinando o crescimento tumoral e consequentemente sua agressividade. O presente estudo teve como objetivo avaliar a ocorrência da apoptose associada a proliferação celular em neoplasias mamárias em cadelas e a elas a evolução clínica do paciente. Setenta animais foram submetidos à exérese cirúrgica do tumor, sendo este submetido ao diagnóstico histopatológico e marcação imuno-histoquímica para caspase-3 e Ki-67. Estes marcadores de apoptose e proliferação celular demonstraram grande expressão nas neoplasias malignas, principalmente nos carcinomas, considerado o mais maligno dos tumores. Estes resultados corroboram os dados da literatura e contribuem para um prognóstico tumoral criterioso que complementa a classificação tumoral existente proporcionando uma melhor e maior sobrevida devido a uma adequação do procedimento terapêutico de cada paciente.
Apoptosis, as a cellular event, has an important participation in tumorigenesis, determining the tumoral growth and aggressiveness. The present study had as objective to evaluate the occurrence of apoptosis, associated cellular proliferation, in canine mammary neoplasias and the patient clinical evolution. Seventy dogs had been submitted to surgical excision of the tumor fragment and they were submitted to the histopathologic diagnosis and imunohistochemistry procedure to caspase-3 and the Ki-67. This apoptosis and cellular proliferation markers demonstrated great expression in malignant neoplasias especially carcinoma, considered the most malignant of the tumors. These results confirm consulted literature contributing for a criterious tumoral prognostic complementing the tumoral classification, providing a greater and better supervened due to adequacy of therapeutic procedure of each patient.