Immunohistochemical and two-parameter flow cytometric studies of DNA topoisomerase II α in human epithelial ovarian carcinoma and germ cell tumor

DNA topoisomerase II α (topo II α) is associated with active cell proliferation and is a target for chemotherapeutic agents administered to patients with ovarian cancer. To evaluate the biologic significance of topo II α expression in human ovarian carcinomas, we examined the expression of this protein immunohistochemically in tissue sections from 99 patients with ovarian cancer (85 common epithelial carcinomas, 14 germ cell tumors). We also measured topo II α and nuclear DNA content by two-parameter flow cytometry in 29 cases to evaluate possible qualitative changes of topo II α in the cell cycle of ovarian cancer cells. We observed a significant correlation of the labeling indices (LIs) of topo II α and Ki-67. The topo II α-to-Ki-67 ratio in germ cell tumors significantly exceeded that in common epithelial ovarian carcinomas (P = .038). Among the latter, the topo II α-to-Ki-67 ratio was significantly higher in serous cystadenocarcinomas than in mucinous cystadenocarcinomas. Two-parameter flow cytometric analysis revealed that topo II α expression was mainly observed in cells at the S to G2/M phases of the cell cycle, but, in some cases, topo II α positivity was detected in cells at G1. A significantly higher topo II α-to-Ki-67 ratio was detected in tumors with topo II α-positive cells at the G1 than in tumors in which topo II α-positive cells were not at GI. Results indicated that quantitative as well as quantitative changes in topo II α occur in human ovarian carcinomas.