Immunohistochemical staining of DNA topoisomerase IIα in human gliomas

Object. The enzyme DNA topoisomerase II alpha (Topo II alpha) was tested as a measure of cell proliferation in gliomas. Methods. Immunostaining for the Topo II alpha 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 II alpha and DNA content. Using flow cytometric analysis, the authors found that the Topo II alpha antibody labeled cells in the S, G(2), and M phases of the cell cycle and also those in some parts of the G(0) and G(1) phases. In histological sections, Topo II alpha 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 IIa correlated highly with one another (r = 0.96). The Topo II alpha 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 II alpha PI less than 5% predicted longer patient survival (p = 0.003). Conclusions. Immunostaining for Topo II alpha represents a useful alternative to MIB-1 as a proliferative index in human gliomas.