Estudo do fator de crescimento endotelial vascular VEGF e da densidade de microvasos em osteossarcomas humanos
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Data
2010-07-29
Autores
Marinho, Larissa Cardoso [UNIFESP]
Orientadores
Alves, Maria Teresa de Seixas [UNIFESP]
Tipo
Tese de doutorado
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INTRODUÇÃO: O papel da angiogênese como indicador prognóstico em câncer é estudado frequentemente e resultados demonstram correlação entre angiogênese e prognostico em neoplasias malignas. Em osteossarcoma poucos estudos foram realizados e permanecem controversos. OBJETIVO: avaliar a densidade de microvasos (MVD) e a expressão do VEGF (vascular endothelial growth factor) como marcadores de angiogenese e a sua correlação com fatores prognósticos. MATERIAL E METODO: blocos de parafina de 50 pacientes pré-quimioterapia ( 22 deles metastáticos ao diagnostico) com osteossarcoma central de alto grau tratados na nossa instituição foram estudados pela técnica de imuno-histoquimica para VEGF e densidade de microvasos determinada por CD 34 e CD 31. A expressão de ambos foi correlacionada com aspectos clinicopatologicos e fatores relacionados ao prognostico (metástases e óbito). As neoplasias foram consideradas positivas para VEGF quando mais que 64,7% (media) das células demonstravam positividade. MVD foi obtida em cada caso pela média de contagem de microvasos em 10 campos de grande aumento (400x) em cada biopsia. Foi considerada alta e baixa usando a media como ponto de corte. RESULTADOS: apesar da alta vascularização não houve significância estatística entre MVD e fatores prognósticos para CD 31 e CD 34. Em relação ao VEGF houve correlação entre VEGF melhor sobrevida global e livre de doença para o total de pacientes. Quando separamos os pacientes metastaticos ao diagnostico os que foram VEGF negativos tiveram melhor sobrevida global e livre de doença. CONCLUSÃO: osteossarcomas são neoplasias bem vascularizadas e a imunoexpressão de VEGF dá informações prognosticas importantes principalmente em pacientes metastaticos ao diagnostico.
INTRODUCTION: The role of angiogenesis as a prognostic indicator in cancer has been extensively studied in recent times with several studies demonstrating a positive correlation for various malignant tumours. However, the role of angiogenesis in osteosarcoma remains a topic of debate. AIM: evaluate the significance of intratumoral microvessel density (MVD) and the degree of vascular endothelial growth factor (VEGF) expression as markers of angiogenesis and correlate with disease outcome. MATERIAL AND METHODS: Pretherapeutic paraffin- embedded biopsies from 50 patients diagnosed high grade central osteosarcoma at our institution with clinicopathological data were studied by immunohistochemical tecnique for VEGF and microvessel density (MVD) determined by CD 34and CD 31expression. VEGF expression and MVD were correlated with clinicopathological factors and patient outcome in terms of metastasis and death. The degree of angiogenesis was assessed, as determined by the microvessel density (MVD). Tumors were considered VEGF positive if immunoexpression was positive in greater than 64,7% ( mean) of the tumor cells. MVD was obtained by microvessels counting 10 high power fields (X400 field) in each biopsy sample. The mean MVD of the entire group was predetermined to classify patients into two groups with high and low MVD.RESULTS: Despite the moderate to high vascularity, there was no significant difference between the MVD and disease outcome factors for both CD 31and CD 34. In terms of VEGF expression, patients with metastases at diagnosis VEGF negative had better overall survival and disease-free survival .CONCLUSION: We were able to demonstrate that osteosarcoma is a relatively vascular tumor and VEGF expression provides prognostic information in osteosarcoma; however, the degree of MVD does not provide prognostic information. Angiogenesis has a potential target for anti-angiogenic therapies.
INTRODUCTION: The role of angiogenesis as a prognostic indicator in cancer has been extensively studied in recent times with several studies demonstrating a positive correlation for various malignant tumours. However, the role of angiogenesis in osteosarcoma remains a topic of debate. AIM: evaluate the significance of intratumoral microvessel density (MVD) and the degree of vascular endothelial growth factor (VEGF) expression as markers of angiogenesis and correlate with disease outcome. MATERIAL AND METHODS: Pretherapeutic paraffin- embedded biopsies from 50 patients diagnosed high grade central osteosarcoma at our institution with clinicopathological data were studied by immunohistochemical tecnique for VEGF and microvessel density (MVD) determined by CD 34and CD 31expression. VEGF expression and MVD were correlated with clinicopathological factors and patient outcome in terms of metastasis and death. The degree of angiogenesis was assessed, as determined by the microvessel density (MVD). Tumors were considered VEGF positive if immunoexpression was positive in greater than 64,7% ( mean) of the tumor cells. MVD was obtained by microvessels counting 10 high power fields (X400 field) in each biopsy sample. The mean MVD of the entire group was predetermined to classify patients into two groups with high and low MVD.RESULTS: Despite the moderate to high vascularity, there was no significant difference between the MVD and disease outcome factors for both CD 31and CD 34. In terms of VEGF expression, patients with metastases at diagnosis VEGF negative had better overall survival and disease-free survival .CONCLUSION: We were able to demonstrate that osteosarcoma is a relatively vascular tumor and VEGF expression provides prognostic information in osteosarcoma; however, the degree of MVD does not provide prognostic information. Angiogenesis has a potential target for anti-angiogenic therapies.
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MARINHO, Larissa Cardoso. Estudo do fator de crescimento endotelial vascular VEGF e da densidade de microvasos em osteossarcomas humanos. 2010. Tese (Doutorado) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2010.