DNA topoisomerase IIalpha protein and mRNA expression in intracranial meningiomas.

Abstract

We examined the expression of DNA topoisomerase IIalpha (Topo IIalpha) immunohistochemically using a monoclonal antibody and compared its proliferative potential [MIB-1 labeling index (LI)] and recurrence to verify the possible influence of Topo IIalpha on the progress of meningiomas. The reverse transcription-polymerase chain reaction (RT-PCR) assay was also performed to evaluate the expression of Topo IIalpha mRNA. Formalin-fixed, paraffin-embedded tissue sections of 52 meningiomas (18 meningothelial types, 16 fibrous types, 4 transitional types, 4 psammomatous types, 1 angiomatous type, 1 secretory type, 5 atypical types, and 3 anaplastic types) were used for immunostaining. The Topo IIalpha labeling index (LI) was 1.4 +/- 1.9% (mean +/- SE) in benign meningiomas and 4.5 +/- 1.6% in atypical or anaplastic meningiomas, representing significant differences between them (P < 0.0001). RT-PCR assay revealed that Topo IIalpha mRNA expression was associated with Topo IIalpha LI. A significant correlation was seen between Topo IIalpha LI and MIB-1 LI (r = 0.517; P < 0.01). Recurrence was significantly more frequent in patients with more than 1.5% of Topo IIalpha LI than in those with 1.5% or less (P < 0.005). In conclusion, Topo IIalpha protein and mRNA expression correlated with clinical malignancy and the potential for predicting the regrowth of meningiomas.