Molecular Biological Determinations of Meningioma Progression and Recurrence

Abstract

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.

Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system

“…In fact, no significant difference in recurrence time was observed between patients with and without loss of 22q. 30,31 Conversely, the association between prognosis and mutations of TRAF7, AKT1, KLF4, and SMO, called the TRAKLS type in this study, have never been investigated. Here we revealed that genotype was associated with recurrence independently from the degree of surgical resection completeness (Simpson grade) and histological malignancy (Ki-67 LI and WHO grade), which is known as prognostic factors in meningioma.…”

Update on Select Benign Mesenchymal and Meningothelial Sinonasal Tract Lesions

“…In contrast to intracranial tumors, gender and age do not influence prognosis. It is noteworthy that features associated with an increased rate of recurrence in CNS meningiomas (increased mitotic activity, loss of architectural pattern, hypervascularity, necrosis, spindle cell formation, nuclear pleomorphism) [77,[83][84][85] are rarely found in sinonasal tract tumors, and when present, are not associated with a worse outcome. If there is death with tumor, it is usually due to involvement of the vital structures of the mid-facial region or to complications of the surgery, rather than to the aggressive nature of the tumor.…”

“…Abnormalities in genes on chromosomes 1p, 6, 9p, 10q, 14q, 17p, 18q and 22 have been described, [77,84,87,88] with deletions of chromosome 22 (monosomy 22) the most consistent cytogenetic alteration. Specifically, these include mutations of the NF2 gene (chromosome 22q12.2), which codes for the protein merlin, a tumor suppressor gene.…”

“…Loss of 1p is the second most common chromosomal abnormality, correlated to ELAVL4 gene which reveals a distinct gender difference [90], and to ALPL (1p36.1-p34) which is down regulated, associated with high grade tumors and recurrence [88]. Several other genes and chromosomes have been elucidated in meningioma, but tend to be associated with Grade II and III tumors or with tumor progression, features not normally present in the sinonasal tract [77,84,87,91].…”

Gene expression profile for predicting survival of patients with meningioma

“…Due to the difficulty of managing meningioma recurrence (2) and the low predictive powers of clinic pathological factors, biomarkers to identify high-risk patients with a poor prognosis are strongly needed. From a previous study conducted in a total 124 samples from 105 patients using the high-resolution FISH-technology (iFISH), it is reported that the deletion of chromosome 1p may be an independent marker of meningioma recurrence and progression (3).…”