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Histopathology ; 61(6): 1006-16, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22804730

RESUMO

AIMS: More than 50% of neuroblastomas (NBs) present with haematogenous and/or lymphatic metastasis; however, little is known about the clinicopathological significance in NBs of the key lymphangiogenesis growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D and the receptor VEGFR-3. METHODS AND RESULTS: Ninety-three NBs and nine ganglioneuromas (GNs) were immunostained for VEGF-C, VEGF-D and VEGFR-3. VEGF-C and VEGF-D were present in 76% and 82% of the NBs, respectively. There was no significant difference in VEGF-C expression between NBs and GNs. VEGF-D expression was significantly higher in NBs compared with GNs and in MYCN-amplified NBs. VEGFR-3 tumoral cell expression (VEGFR-3c), present in 48% of the NBs, was significantly higher in NBs from children ≥ 18 months at presentation and those belonging to a high-risk group. VEGFR-3 lymphovascular density was increased significantly in NBs compared with GNs and in NBs associated with adverse clinicopathological and biological factors. Lymphovascular invasion, assessed in VEGFR-3-stained vessels, was present in ∼50% of NBs. Cox regression analyses demonstrated that VEGFR-3c expression was associated with a significantly shorter event-free survival and that its effect was independent of the important pathological variable, mitosis-karyorrhexis index. CONCLUSIONS: VEGF-D and VEGFR-3 up-regulation support tumour progression in NB and VEGFR-3c may provide a useful prognostic marker in NBs.


Assuntos
Biomarcadores Tumorais/metabolismo , Neuroblastoma/metabolismo , Neoplasias do Sistema Nervoso Periférico/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator D de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Ganglioneuroma/diagnóstico , Ganglioneuroma/metabolismo , Ganglioneuroma/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Linfangiogênese/fisiologia , Neuroblastoma/diagnóstico , Neuroblastoma/mortalidade , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Neoplasias do Sistema Nervoso Periférico/mortalidade , Prognóstico , Estudos Retrospectivos , Regulação para Cima , Fator C de Crescimento do Endotélio Vascular/genética , Fator D de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética
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