Molecular biological determinations of meningioma progression and recurrence.
Meningiomas are tumors that arise from the coverings of the brain or spinal cord. 5% of the cases turn into malignant forms with aggressive clinical behavior and increased risk of tumor recurrence. One hundred and five patients with meningiomas were operated by open surgery. To investigate predictors of meningioma recurrence in total 124 samples of 105 patients were investigated by iFISH. Dual-probe hybridization was performed to access chromosomal alterations of chromosomes 1p-, 9p- and 22q. Additionally, methylation of TIMP3 and p16 was analyzed with MS-PCR. Of the 105 investigated tumors 59.1% (62/105) were WHO grade I, 33.3% (35/105) were WHO grade II and 7.7% (8/105) were anaplastic meningiomas (grade III), respectively. The histopathological data correlates with the recurrence rate of the investigated meningiomas. Hypermethylation of TIMP3 was detected in 13.3% of all meningiomas: 10.9% in WHO grade I meningiomas, 25.0% in grade II and 14.3% in grade III meningiomas, respectively. No correlation of TIMP3 hypermethylation with tumor recurrence or WHO grade (p = 0.2) was observed. Interestingly, deletion of 1p36 emerged as a significant predictor of shorter overall survival (log rank test, p<0.001), whereas TIMP3 promoter methylation had no significant effect on overall survival (log rank test, p = 0.799). The results of the current study support the finding that the deletion of chromosome 1p is an independent marker of meningioma recurrence and progression (p = 0.0097). Therefore the measurement of genetic aberrations in meningiomas allows in a combined histological approach a more precise assessment of the prognosis of meningiomas than histopathology alone.
Department of Neurosurgery, Saarland University, Homburg/Saar, Germany.
Stefan
S
Linsler
Department of Neurosurgery, Saarland University, Homburg/Saar, Germany.
Dennis
D
Kraemer
Department of Neurosurgery, Saarland University, Homburg/Saar, Germany.
Christina
C
Driess
Department of Neurosurgery, Saarland University, Homburg/Saar, Germany.
Joachim
J
Oertel
Department of Statistics, TU Dortmund University, Dortmund, Germany; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Kai
K
Kammers
Department of Statistics, TU Dortmund University, Dortmund, Germany.
Jörg
J
Rahnenführer
Department of Neurosurgery, Saarland University, Homburg/Saar, Germany.
Ralf
R
Ketter
Department of Neurosurgery, Saarland University, Homburg/Saar, Germany.
Steffi
S
Urbschat
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics
C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3