Aim: The aim of our study was to evaluate the frequency of deletions on chromosomes 1, 9, 10, 14, 18 and 22 in 75 benign and 15 atypical meningiomas and correlate them with clinical findings. Methods: Paired normal and tumour DNA samples obtained from the patients operated on, were analyzed for loss of heterozygosity (LOH), using 24 microsatellite markers and PCR techniques. Results: Statistical analysis showed that deletions on chromosomes 14 and 18 were significantly associated with WHO grade of the meningiomas (p=0.048 and p=0.03, respectively). In addition, LOH on chromosome 14 was significantly associated with tumour size (p=0.048), as the risk of developing a tumour larger than 4 cm in diameter was 6-times greater than the risk of developing tumour with diameter below 4 cm. The most frequent genetic abnormality in meningiomas is 22 LOH, which was confirmed in the present study in which high frequency of such abnormality was observed (66%). There was a clear associations between chromosome 22 status and histological subtype. LOH on chromosome 22 was more frequent in fibrous meningiomas than in the meningothelial variant (p=0.001). Besides that, there was a relationship between 22 LOH status and tumour location: the frequency of LOH in skull base meningiomas was significantly lower compared to parasagittal meningiomas (p=0.0004). Conclusions: These results indicated that allelic loss on chromosomes 9, 10, 14, 18 and 22 may be associated with meningioma pathogenesis and progression.
Atypical meningiomas are defined according WHO criteria as tumours characterized by: increased mitotic activity or three or more of the following histologic features: increased cellularity, small cells with a high nuclear/cytoplasmic ratio, prominent nucleoli, patternless or sheet like growth, and foci of “spontaneous” or “geographic” necrosis. It means, that those meningiomas which reveal only one or even two from above mentioned features are, according to WHO classification, still consistent with diagnosis of benign (GI WHO) tumours. Histologic slices from 65 atypical meningiomas were investigated and presence of each from those diagnostic histologic criteria which were mentioned above, were taken to account. Additionally, in the same way 59 benign meningiomas, which showed one or two histologic features characteristic for atypical type of the tumours, were analysed. In all cases immunohistochemical reaction with MIB-1 antibody was carried out and proliferating indices (PI) were established using image analysis computer system. Correlation between histologic criteria for atypical meningiomas and proliferating indices of the tumours was statistically estimated. We found a significant relationship between PI and mitotic activity, necrosis, small cells changes, patternless growth, nucleolies and number of histologic features that tumors present.