PROLIFERATION AND DNA FRAGMENTATION IN MENINGIOMA SUBTYPES

Atypical meningioma has been introduced as tumour subtype of intermedi ate biological behaviour between classical and malignant meningiomas. To substantiate this three-step scale of malignancy, we assessed the p roliferative activity reflected by Ki-67 (MIB1) labelling index (LI) i n a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningio mas. The possible correlation of proliferation with the frequency of a poptosis and their relations to BCL-2 immunoexpression was investigate d in seven classical, 10 atypical and 10 malignant meningiomas. Apopto sis was demonstrated by evaluation of the frequency of apoptotic figur es, by the enzymatic technique of in situ tailing (IST) which stains a poptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas. MI B1 LI revealed a highly significant increase from classical through at ypical to anaplastic meningiomas (P < 0.0001); haemangiopericytomas an d papillary meningiomas were well within the range of atypical meningi omas. 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 wit h malignancy grade and was unrelated to MIB1 LI or frequency of apopto sis. Our data show that (i) apoptosis is a feature of meningiomas, sig nificantly correlated with the malignancy scale, (ii) DNA fragmentatio n shows significant correlation with proliferation and inversely with BCL-2 expression; (iii) proliferation indices and frequencies of apopt osis/DNA fragmentation within meningioma subgroups corroborate the int ermediate biological position of the atypical meningioma between class ical and malignant meningiomas.