Immunohistochemical staining of DNA topoisomerase IIα in human gliomas

Abstract

Object. The enzyme DNA topoisomerase IIα (Topo IIα) was tested as a measure of cell proliferation in gliomas.Methods. Immunostaining for the Topo IIα and for the Ki-67 antigen (MIB-1 antibody) was performed in paraffin-embedded tissue sections obtained from 25 resected human gliomas. Additionally, cultured human glioma cells were subjected to simultaneous flow cytometry to determine Topo IIα and DNA content.Using flow cytometric analysis, the authors found that the Topo IIα antibody labeled cells in the S, G2, and M phases of the cell cycle and also those in some parts of the G0 and G1 phases. In histological sections, Topo IIα showed more distinct staining than MIB-1, particularly in older archival cases. The proliferative indices (PIs) based on cells staining for MIB-1 and Topo IIα correlated highly with one another (r = 0.96). The Topo IIα PI immunopositivity was seen in 4.07% of cells in the low-grade astrocytoma group, 11.97% in the anaplastic astrocytoma group, and 13.84% in the glioblastoma multiforme group, representing significant differences between low-grade astrocytoma and both anaplastic astrocytoma and glioblastoma. A Topo IIα PI less than 5% predicted longer patient survival (p = 0.003).Conclusions. Immunostaining for Topo IIα represents a useful alternative to MIB-1 as a proliferative index in human gliomas.