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Topoisomerase II-α (topo IIα) is the key target enzyme for the topoisomerase inhibitor class of anti-cancer drugs. In normal cells, topo IIα is expressed predominantly in the S/G2/M phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo IIα is both higher and less dependent on proliferation state in the cell. We studied fresh specimens from 50 cases of primary breast cancer. The expression of topo IIα in different cell cycle phases was analyzed with two-parameter flow cytometry using the monoclonal antibody SWT3D1 and propidium iodide staining. The expression of topo IIα was significantly higher in the S/G2/M phase of the cell cycle than in the G0/G1 phase in both DNA diploid and DNA nondiploid tumors. In 18 of 21 diploid tumors, and in 25 of 29 nondiploid tumors,> 50% of the topo IIα–positive cells were in the G0/G1 phase. This significant expression of topo IIα in the …