High expression of cathepsin B and plasminogen activator inhibitor type-1 are strong predictors of survival in glioblastomas
| Autor: | Olivier Chinot, Dominique Intagliata, Frédéric Fina, Dominique Figarella-Branger, Janko Kos, L'Houcine Ouafik, Tamara T. Lah, Philippe Metellus, Corinne Bouvier, Anderson Loundou, N. Baeza, Brigitte Voutsinos-Porche, Carole Colin, Christine Delfino, Pierre-Marie Martin, Isabelle Nanni |
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| Přispěvatelé: | Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Département de Neurochirurgie [CHU Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Service d’Anatomopathologie, Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Département de neurooncologie, Faculty of Pharmacy, University of Ljubljana |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Proteases
Pathology medicine.medical_specialty MMP2 medicine.medical_treatment [SDV.CAN]Life Sciences [q-bio]/Cancer In situ hybridization MMP9 Biology Cathepsin B Statistics Nonparametric Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Invasion process Plasminogen Activator Inhibitor 1 medicine Biomarkers Tumor Humans neoplasms In Situ Hybridization ComputingMilieux_MISCELLANEOUS Aged Aged 80 and over Protease Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Prognosis Immunohistochemistry nervous system diseases 030220 oncology & carcinogenesis Neurology (clinical) Glioblastoma 030217 neurology & neurosurgery |
| Zdroj: | Acta Neuropathologica Acta Neuropathologica, Springer Verlag, 2009, 118 (6), pp.745-754. ⟨10.1007/s00401-009-0592-2⟩ |
| ISSN: | 0001-6322 1432-0533 |
| DOI: | 10.1007/s00401-009-0592-2⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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