gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

uPA/PAI-1 expression and uPA promoter methylation in meningiomas

Meeting Abstract

  • J. Kandenwein - Neurochirurgische Klinik, Universitätsklinikum Bonn
  • T.W. Park-Simon - Frauenklinik, Medizinische Hochschule Hannover
  • R. Mahlberg - Neurochirurgische Klinik, Universitätsklinikum Bonn
  • J. Schramm - Neurochirurgische Klinik, Universitätsklinikum Bonn
  • M. Simon - Neurochirurgische Klinik, Universitätsklinikum Bonn

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocMO.11-01

DOI: 10.3205/09dgnc071, URN: urn:nbn:de:0183-09dgnc0718

Published: May 20, 2009

© 2009 Kandenwein et al.
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Outline

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Objective: The degree of resection and the intrinsic biological aggressiveness of the tumor have been repeatedly identified as the primary determinants of meningioma recurrence. Invasive growth limits the resectability of meningiomas. Brain invasion has been included as a grading criterion into the 2007 WHO classification. Tumor invasion is mediated by matrix metalloproteases and their inhibitors such as uPA and PAI-1. For the present paper, we have investigated the role of uPA/PAI-1 expression and methylation of the uPA promoter in meningiomas.

Methods: 65 tumor tissue samples (WHO grade I: 26, grade II: 27, grade III: 12) from 58 patients (including 5 patients with multiple synchronous tumors, 2 patients with primary and recurrent tumor, and altogether 14 patients with recurrent tumors) were analyzed for uPA and PAI-1 protein content using a commercially available ELISA kit (Femtelle, American Diagnostica GmbH, Pfungstadt). For uPA promoter methylation analysis, a 365bp promoter fragment was PCR amplified after bisulfite treatment and subjected to a methylation-sensitive restriction digest with AciI. Pertinent clinical data were retrieved from the patients’ charts.

Results: Variable levels of uPA (mean: 0.42±0.61, median: 0.2, range: 0.06–4.58 ng/mg total protein) and PAI-1 protein (mean: 30.2±102.3, median: 5.7, range: 0.7–625 ng/mg total protein) were detected in the meningioma samples. Methylation of the uPA promoter did not correlate with uPA expression. uPA and PAI-1 protein expression correlated significantly with the WHO grade (uPA: p=0.034, PAI-1: p<0.001). High (> median) PAI-1 levels were seen more frequently in tumors with brain invasion (p=0.002). Higher levels of uPA promoter methylation (PCR signal of methylated DNA > signal of non-methylated DNA) were more often seen in recurrent tumors (p=0.027). No correlations between tumor size, location (convexity vs. skull base), bone invasion, multiplicity and uPA/PAI-1 expression or uPA promoter methylation were observed.

Conclusions: Our data suggest potential associations between uPA/PAI-1 expression and uPA promoter methylation and the histological grade of meningiomas, brain invasion, and tumor recurrence. Our findings also indicate that uPA expression is not primarily regulated by promoter methylation. Further studies of the role of uPA/PAI-1 and uPA promoter methylation in meningiomas seem warranted.