Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype.

作者: Gheeyoung Choe , Lisa Jouben-Steele , Paul S. Mischel , Harry V. Vinters , Thomas J. Kremen

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摘要: Purpose: Glioblastoma multiforme (GBM) is an aggressive cancer characterized by extensive brain invasion. Matrix metalloproteinase (MMP)-9 plays a major role in this process. GBMs can be divided into two subtypes based on distinct clinical and molecular features. Primary arise de novo frequently overexpress the epidermal growth factor receptor (EGFR) its ligand-independent variant, EGFR variant III (EGFRvIII); secondary progress from lower grade glioma commonly harbor p53 mutations. Because signaling promotes MMP-9 expression activation other cell types, we analyzed whether was associated with primary GBM subtype. Experimental Design: Autopsies were performed 20 patients, MMP assessed gelatin zymography tumor adjacent normal brain. EGFR, EGFRvIII, p53, activated mitogen-activated protein kinase/extracellular signal-regulated kinase immunohistochemistry, associations between phenotype analyzed. Results: Latent detected 90% of tumors, active found 50% tumors. not any samples ( P = 0.027). Active observed 73% EGFR-overexpressing/wild-type p53-staining tumors but only 20% EGFR-negative/aberrant 0.072). even more strongly correlated EGFRvIII expression, occurring 83% EGFRvIII-immunopositive none EGFRvIII-negative 0.0004). Extracellular also 0.003). Conclusions: These results identify novel association subtype suggest that especially those whose express may benefit anti-MMP therapy.

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