Journal
ACTA NEUROPATHOLOGICA
Volume 118, Issue 6, Pages 745-754Publisher
SPRINGER
DOI: 10.1007/s00401-009-0592-2
Keywords
Glioblastomas; Invasion process; Cathepsin B; PAI-1; Proteases; Prognostic biomarker
Categories
Funding
- INCA [RS019]
- Societe Francaise de lutte contre les Cancers et les leucemies de l'Enfant et de l'adolescent (SFCE)
- Association pour la Recherche sur les Tumeurs Cerebrales
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In contrast to pilocytic astrocytomas (WHO grade I gliomas) that are circumscribed and cured by surgical resection, invasion is a hallmark of grades II-IV gliomas. Proteases play a major role in the invasion process and correlations between glioma grading, survival and protease expression have been demonstrated. In this study, we have chosen to study using different technical approaches (Q-RT-PCR, in situ hybridization and immunohistochemistry) the expression of five molecules involved in extracellular matrix degradation (cathepsin B, MMP2, MMP9, uPA and PAI-1) in glioblastomas in order to determine their prognostic impact among grade IV gliomas. Pilocytic astrocytomas were used as controls. Q-RT-PCR showed that transcripts of uPA, PAI-1, cathepsin B and MMP9 were significantly more expressed in glioblastomas (n = 52), in comparison to pilocytic astrocytomas (n = 17) (P = 0.049, P < 0.0001, P = 0.03 and P < 0.0001, respectively). On both univariate and multivariate analyses, cathepsin B and PAI-1 were strong predictors of overall survival among the group of glioblastomas (P < 0.0001 and P = 0.01, respectively). Immunohistochemical expression of cathepsin B further confirmed its prognostic value in an independent cohort of patients with glioblastoma. In situ hybridization showed that uPA is detected at the invasive edge of glioblastomas, whereas PAI-1 is more abundant in microvascular proliferation and pseudo-palisading cells than at the infiltrative edges. These results suggest that cathepsin B and PAI-1 are important biomarkers for the stratification of glioblastoma patients with respect to survival.
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