Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma

AIM: Matrix metalloproteinase (MMP)-14 and MMP-19 have been demonstrated to play an important role in the development of human gliomas. However, their prognostic values are not clear. The aim of this study was to investigate whether co-expression of MMP-14 and MMP-19 has prognostic relevance in human gliomas. METHODS: Immunohistochemistry and western blot were used to investigate the expression of MMP-14 and MMP-19 proteins in 128 patients with gliomas. RESULTS: The expression levels of MMP-14 and MMP-19 proteins in glioma tissues were both significantly higher (both P < 0.001) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis, which was confirmed by the western blot analysis. Additionally, the overexpression of either MMP-14 or MMP-19 was significantly associated with the advanced WHO grade (both P = 0.02), the low Karnofsky performance score (KPS) (P = 0.008 and 0.01, respectively) and the poor overall survival (both P = 0.01). Moreover, the Multivariate Cox proportional-hazards regression analysis revealed that the increased expressions of MMP-14 and MMP-19 were both independent prognostic factors for poor overall survival (both P = 0.02). Furthermore, the co-expression of MMP-14 and MMP-19 was additively and more significantly (P = 0.006) associated with adverse prognosis in patients with gliomas than respective expression of MMP-14 and MMP-19. CONCLUSIONS: These findings indicated for the first time that the co-expression of MMP-14 and MMP-19 is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker (AU)

Bases patogénicas de la epileptogénesis en los cavernomas cerebrales / Pathogenetic bases of epileptogenesis in cerebral cavernomas

Introducción. Los cavernomas cerebrales son un tipo de malformación arteriovenosa que cursa clínicamente con crisis epilépticas, déficits neurológicos focales y hemorragias intraparenquimatosas. Se cree que las situaciones de hipoxia, neovascularización y algunas endoproteasas están implicadas en la fisiopatología de las crisis. Nuestro estudio pretende valorar esta posible relación, analizando con métodos inmunohistoquímicos la presencia de la subunidad 1α del factor inducible por hipoxia (HIF-1α) y la metaloproteasa de matriz 9 (MMP-9). Pacientes y métodos. Se seleccionaron 17 muestras consecutivas con diagnóstico anatomopatológico de cavernoma en un período de nueve años sobre las que se realizó una tinción inmunohistoquímica para HIF-1α y MMP-9, valorando la relación con las crisis epilépticas según el grado de captación del anticuerpo de los diferentes tejidos encontrados alrededor de las muestras de cavernoma. Resultados. En aquellos pacientes que presentaron crisis, se observó tinción inmunohistoquímica para HIF-1α en el 31% de las muestras en el endotelio vascular, el 17% en el tejido fibroso y el 34% en el tejido inflamatorio. También se observó tinción positiva para MMP-9 en el 86% del endotelio vascular, el 100% del tejido fibroso y el 43% del tejido cerebral. Analizando la muestra, se observa una tendencia positiva en presencia de crisis epilépticas en los pacientes que muestran la presencia de HIF-1α y MMP-9 en el endotelio vascular, tejido fibroso y tejido cerebral, no siendo así para el tejido inflamatorio. Conclusión. La expresión de HIF-1α y MMP-9, evaluada por métodos inmunohistoquímicos, se relaciona positivamente con la presencia de complicaciones de tipo epiléptico (AU)

Introduction. Brain cavernoma are a type of arteriovenous malformation that clinically presenting seizures, neurological deficit or bleeding. Hypoxia, neoangiogenesis and metalloproteasas seems to be involved in seizures physiopathology. Our study aims to assess this potential relation by immunohistochemical methods, analyzing hypoxia inducible factor (HIF-1alpha) and metalloproteasa (MMP-9) in tissue surrounding cavernoma. Patients and methods. We selected 17 consecutive cases anatomopathologically diagnosed as cavernoma during 9 years. Immunohistochemical staining was performed for HIF-1alpha and MMP-9. We evaluated the relation between seizures and the scale of uptake of different tissues surrounding cavernoma. Results. Cases with seizures had HIF-1alpha positive uptake in vascular endothelium in 31%, 17% in fibrous tissue and 34% in inflammatory tissue. Besides, it also shows MMP-9 positive uptake in vascular endothelium in 86%, 100% in fibrous tissue and 43% of brain tissue. Statistical analysis by chi-square and odds ratio shows a positive trend towards seizures and the presence of HIF-1alpha and MMP-9 in vascular tissue, fibrous tissue and brain tissue, but no for inflammatory tissue. Conclusion. HIF-1alpha and MMP-9, valued by immunohistochemical methods, are related to complications as seizures (AU)