gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

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Detection of TIMP-3 promoter hypermethylation and its prognostic significance in meningiomas

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  • S. Linsler - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg
  • S. Urbschat - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg
  • C. Driess - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg
  • D. Krämer - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg
  • C. Lerner - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg
  • J. Oertel - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg
  • R. Ketter - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocP 097

doi: 10.3205/12dgnc484, urn:nbn:de:0183-12dgnc4847

Published: June 4, 2012

© 2012 Linsler et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Objective: Meningiomas are tumors that arise from the coverings of the brain or the spinal cord. They are mostly benign. However, in about 5% of the cases, they turn into malignant forms with aggressive clinical behavior and increased risk of tumor recurrence. Meningiomas are cytogenetically well characterized, with normal karyotype or monosomy of chromosome 22. The tissue inhibitor of metalloproteinase-3 (TIMP-3) maps on the long arm of chromosome 22 in the region 22q12. TIMP-3 has an inhibitory effect on tumor development and growth due to its interaction with matrix metalloproteinases. We investigated the prognostic significance of TIMP-3 gene promoter methylation in correlation to cytogenetic marker of progression in meningioma.

Methods: 127 meningioma patients were operated by open surgery. Tissue specimens from tumors were obtained after surgery and prepared for FISH analysis. According to our previous results we used two color FISH for chromosomal alterations of chromosome 1p and 22. Additionally, methylation of TIMP3 were analysed with MS-PCR. T-test and Pearson correlation were used for statistical analysis.

Results: 46% (57/127) of the investigated tumors were WHO I, 45% (56/127) WHO II and 10% (12/127) WHO III meningiomas. The average age of all patients was 56 years (±14), 55 years (±13) of the female patients (87/127) and 57 years (±17) of the male patients (40/127). We found hypermethylation of TIMP3 in 17% (2/12) of WHO III meningiomas, in 14% (8/56) of WHO II and in 14% (8/57) of WHO I meningiomas. The hypermethylation of TIMP3 correlates well to deletion on 1p (p<0.05). In case of recurrent meningiomas (24/127) we found in 16% (4/24) hypermethylation of TIMP3.

Conclusions: These results demonstrate that TIMP-3 hypermethylation is associated with higher histological grades. Also it is even more correlated to the marker of cytogenetic progression as i.e. deletion of chromosome 1p – as most important genetic aberration in meningiomas – and might therefore serve as a marker of progression in histological inconspicuous meningiomas.