DNA topoisomerase II-alpha as a proliferation marker in astrocytic neoplasms of the central nervous system: correlation with MIB1 expression and patient survival.

Abstract

DNA topoisomerase II-alpha (topo II-alpha) is the target of a variety of clinically used anticancer drugs such as etoposide, teniposide, and doxorubicin. The enzyme has also been used as a cell proliferation marker. Because proliferation measurements in central nervous system (CNS) astrocytic neoplasms have been shown to have prognostic importance and because drugs targeting topo II-alpha may be useful in treating these tumors, we determined topo II-alpha expression in 26 patients with CNS astrocytomas. In these tumors, topo II-alpha expression correlated well with the known proliferation marker, MIB1 (correlation coefficient = 0.94). Topo II-alpha expression also correlated with the histologic classification of the tumor. Grade 1 lesions had an average topo II-alpha index of 2.1 (range, 0 to 3.4); grade 2 lesions, 4.0 (range, 0 to 11.4); grade 3 lesions, 17.3 (range, 3.8 to 69.8); and grade 4 lesions (glioblastoma multiforme), 39.5 (range, 14.8 to 84.0). The average topo II-alpha and MIB1 index of patients alive two years after diagnosis was 8.8 (range, 0 to 45.6) and 11.8 (range, 0.2 to 44.0), respectively. In contrast, the average topo II-alpha and MIB1 index of 30.5 (range, 2.8 to 69.8) and 33.8 (range, 2.2 to 84.6), respectively, was observed in tumors from patients who were dead from disease by two years. The topo II-alpha index between patients alive and dead at two years was statistically different at the 95% confidence level. The MIB1 differences between these two groups of patients was not found to be statistically different.