Investigação e validação de fatores prognósticos em hemangiossarcomas esplênicos caninos.
Carregando...
Arquivos
Data
2020-10-01
Autores
Rozolen, Juliana Moreira
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O hemangiossarcoma (HSA) é um tumor maligno das células endoteliais e apresenta comportamento biológico agressivo. Afetam cães de meia idade a idosos e são caracterizados pela formação de novos vasos associados a áreas necróticas e hemorrágicas. Pacientes com HSA esplênico apresentam sintomas como anorexia, distensão abdominal e ruptura esplênica aguda causando óbito em um curto período. Na medicina veterinária, vários estudos avaliaram retrospectivamente a sobrevida global em cães afetados por HSA ou investigaram a expressão de genes e proteínas de diferentes marcadores em amostras de necropsia ou cultura de células. No entanto, um número limitado de estudos combinou ambas as estratégias para identificar novos fatores prognósticos. Conhecendo o potencial de sobrevida e os correlacionando com possíveis marcadores, podemos desenvolver um painel prognóstico e assim, torna-los futuros alvos terapêuticos. Portanto esta pesquisa teve como objetivo associar critérios clínicopatológicos, Claudin-5, PSMA e Ki67 expressão gênica e proteica de à sobrevida global em pacientes afetados pelo HSA. Cinquenta e três amostras de HSA esplênicos previamente diagnosticados por exame histopatológico foram utilizadas nesta pesquisa. A expressão proteica de Claudin-5, PSMA e Ki-67 foram avaliadas pelas técnicas de imuno-histoquímica e a expressão gênica de Claudin-5 e PSMA foram avaliadas por qPCR. As amostras foram classificadas histologicamente em cavernoso (n=23), capilar (n=16) e sólido (n=14). Os marcadores foram superexpressos em amostras de pacientes com metástase em associação ao estádio tumoral. Entretanto, o subtipo sólido apresentou um índice proliferativo mais alto em relação aos demais subtipos histológicos. Identificou-se também um maior índice proliferativo em tumores indiferenciados quando comparados aos HSA esplênicos diferenciados. Nosso estudo confirmou que pacientes com estádio III e doença metastática apresentaram um pior prognostico. A quimioterapia adjuvante proporciona maior sobrevida global para os pacientes e deve ser indicada para os pacientes com HSA esplênico.
Splenic hemangiosarcoma (HSA) is a malignant tumor from endothelial cells, with aggressive biological behavior. They affect middle-aged and elderly dogs and are characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas, leading patients to clinical symptoms of anorexia, abdominal distension and severe acute rupture with death in a short period. Several studies have retrospectively evaluated overall survival in HSA-affected dogs or investigated gene and protein expression of different markers in necropsy samples or cell culture. However, a limited number of studies combined both strategies to identify new prognostic factors. Knowing potential survival and correlating it with possible markers we can develop a prognostic panel and thus make them a future therapeutic target. Thus, this research aimed to associate the clinical-pathological findings, PSMA, Claudin-5 and Ki67gene 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 research. Claudin-5, PSMA and KI67 protein expression was evaluated by immunohistochemistry and the gene expression by qPCR. Histological classification identified were cavernous (n= 23), capillary (n= 16) and solid (n= 14). Markers were overexpressed in samples from patients with metastasis and there were also association with tumor stage. However, solid subtype showed a higher proliferative index when compared to others subtype. It was also identified a higher proliferative index in undifferentiated tumors when compared to differentiated splenic HSA. Our study has confirmed that patients with stage III and metastatic disease present a poor prognosis. The adjuvant chemotherapy provides a higher overall survival for the patients and should indicated for all patients with splenic HSA.
Splenic hemangiosarcoma (HSA) is a malignant tumor from endothelial cells, with aggressive biological behavior. They affect middle-aged and elderly dogs and are characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas, leading patients to clinical symptoms of anorexia, abdominal distension and severe acute rupture with death in a short period. Several studies have retrospectively evaluated overall survival in HSA-affected dogs or investigated gene and protein expression of different markers in necropsy samples or cell culture. However, a limited number of studies combined both strategies to identify new prognostic factors. Knowing potential survival and correlating it with possible markers we can develop a prognostic panel and thus make them a future therapeutic target. Thus, this research aimed to associate the clinical-pathological findings, PSMA, Claudin-5 and Ki67gene 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 research. Claudin-5, PSMA and KI67 protein expression was evaluated by immunohistochemistry and the gene expression by qPCR. Histological classification identified were cavernous (n= 23), capillary (n= 16) and solid (n= 14). Markers were overexpressed in samples from patients with metastasis and there were also association with tumor stage. However, solid subtype showed a higher proliferative index when compared to others subtype. It was also identified a higher proliferative index in undifferentiated tumors when compared to differentiated splenic HSA. Our study has confirmed that patients with stage III and metastatic disease present a poor prognosis. The adjuvant chemotherapy provides a higher overall survival for the patients and should indicated for all patients with splenic HSA.
Descrição
Palavras-chave
Imuno-histoquímica, Neoplasia endotelial esplênica, Marcadores gênicos, Índice proliferativo., Immunohistochemistry, Endothelial splenic neoplasia, Gene markers, Proliferative index