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Proliferation and DNA fragmentation in meningioma subtypes
H Maier1, J Wanschitz, R Sedivy
1Institute of Neurology, University of Vienna, Austria.
Abstract:
Atypical meningioma has been introduced as tumour subtype of intermediate biological behaviour between classical and malignant meningiomas. To substantiate this three-step scale of malignancy, we assessed the proliferative activity reflected by Ki-67 (MIB1) labelling index (LI) in a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningiomas. The possible correlation of proliferation with the frequency of apoptosis and their relations to BCL-2 immunoexpression was investigated in seven classical, 10 atypical and 10 malignant meningiomas. Apoptosis was demonstrated by evaluation of the frequency of apoptotic figures, by the enzymatic technique of in situ tailing (IST) which stains apoptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas. MIB1 LI revealed a highly significant increase from classical through atypical to anaplastic meningiomas (P < 0.0001); haemangiopericytomas and papillary meningiomas were well within the range of atypical meningiomas. IST indices rose with increasing malignancy and correlated with MIB1 LI (P < 0.0001): they showed a weak inverse correlation with BCL-2 immunoexpression (P = 0.05). BCL-2 expression tended to decrease with malignancy grade and was unrelated to MIB1 LI or frequency of apoptosis. Our data show that (i) apoptosis is a feature of meningiomas, significantly correlated with the malignancy scale. (ii) DNA fragmentation shows significant correlation with proliferation and inversely with BCL-2 expression; (iii) proliferation indices and frequencies of apoptosis/DNA fragmentation within meningioma subgroups corroborate the intermediate biological position of the atypical meningioma between classical and malignant meningiomas.
Insights
Atypical meningiomas bridge classical and malignant types, with proliferation and apoptosis correlating with malignancy. This study confirms atypical meningiomas' intermediate biological behavior.
Area of Science:
- Neuro-oncology
- Tumor Biology
- Pathology
Background:
- Atypical meningioma is considered an intermediate tumor subtype.
- Understanding its biological behavior is crucial for accurate grading.
Purpose of the Study:
- To validate the three-step malignancy scale of meningiomas.
- To assess the correlation between proliferation (Ki-67), apoptosis, and BCL-2 expression in meningiomas.
Main Methods:
- Assessed Ki-67 (MIB1) labeling index in 89 meningiomas.
- Investigated apoptosis using apoptotic figures, in situ tailing (IST), and DNA laddering.
- Examined BCL-2 immunoexpression.
Main Results:
- Ki-67 labeling index significantly increased from classical to anaplastic meningiomas.
- Apoptosis frequency and IST indices correlated positively with malignancy and Ki-67 LI.
- BCL-2 expression showed a weak inverse correlation with apoptosis and decreased with malignancy.
Conclusions:
- Apoptosis is a significant feature of meningiomas, correlating with malignancy grade.
- Proliferation and apoptosis data support the intermediate biological position of atypical meningiomas.
- Atypical meningiomas represent a distinct entity between classical and malignant types.