Immunohistochemical staining of DNA topoisomerase IIalpha in human gliomas

J Neurosurg. 1999 Sep;91(3):477-82. doi: 10.3171/jns.1999.91.3.0477.


Object: The enzyme DNA topoisomerase IIalpha (Topo IIalpha) was tested as a measure of cell proliferation in gliomas.

Methods: Immunostaining for the Topo IIalpha 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 IIalpha and DNA content. Using flow cytometric analysis, the authors found that the Topo IIalpha 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 IIalpha 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 IIalpha correlated highly with one another (r = 0.96). The Topo IIalpha 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 IIalpha PI less than 5% predicted longer patient survival (p = 0.003).

Conclusions: Immunostaining for Topo IIalpha represents a useful alternative to MIB-1 as a proliferative index in human gliomas.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Neoplasm / analysis*
  • Astrocytoma / enzymology
  • Astrocytoma / pathology
  • Biomarkers, Tumor / analysis
  • Cell Division
  • Child
  • Coloring Agents
  • DNA Topoisomerases, Type II* / analysis*
  • DNA, Neoplasm / analysis
  • DNA-Binding Proteins
  • Female
  • Flow Cytometry
  • G1 Phase
  • G2 Phase
  • Glioblastoma / enzymology
  • Glioblastoma / pathology
  • Glioma / enzymology*
  • Glioma / pathology
  • Humans
  • Immunohistochemistry
  • Isoenzymes / analysis*
  • Ki-67 Antigen / analysis
  • Male
  • Middle Aged
  • Mitosis
  • Paraffin Embedding
  • Resting Phase, Cell Cycle
  • S Phase
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Coloring Agents
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Isoenzymes
  • Ki-67 Antigen
  • DNA Topoisomerases, Type II