Robert D. Fleischmann

Human DNA topoisomerase I alpha

DNA topoisomerase II-alpha (topo II-alpha) is the molecular target of several types of clinically useful anticancer drugs such as etoposide, teniposide, doxorubicin, and mitoxantrone. The enzyme is also a proliferation marker in normal cells and tissues. High levels of enzyme are present in the S and G2 phases of the cell cycle. New data are emerging which suggest that anticancer drugs which target the topoisomerases may be useful in the treatment of patients with ovarian neoplasms. However, there is relatively little data on the expression of these enzymes in human ovarian cancer. We have recently developed an in situ immunohistochemical stain which can detect the presence of topo II-alpha in formalin-fixed paraffin-embedded human tissue sections. In order to determine topo II-alpha levels in ovarian tumors, we immunostained for topo II-alpha, 30 ovarian neoplasms which ranged from benign to highly malignant. We correlated our results with expression of MIB1 in order to determine if topo II-alpha expression correlates with cell proliferation. Since the gene for topo II-alpha is closely linked to the gene for the c-erbB-2 oncogene, we also evaluated the cases for amplification of c-erbB-2. Our results indicate that topo II-alpha correlates well with MIB1 indicating that topo II-alpha may be useful in estimating cell proliferation in ovarian tumors. In addition, 1 of 15 patients with a malignant neoplasm had a carcinoma which expressed high levels of topo II-alpha. Since the sensitivity of cells to topo II targeted drugs is dependent on high topo II levels, this suggests that topo II-alpha immunostaining in ovarian cancer may also identify a subset of patients potentially treatable with topo II targeted drugs. None of the ovarian neoplasms showed amplification of c-erbB-2.