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P-Glycoprotein Expression and DNA Topoisomerase I and II Activity in Benign Tumors of the Ovary and in Malignant Tumors of the Ovary, before and after Platinum/Cyclophosphamide Chemotherapy¹

Division of Gynecologic Oncology, Department of Gynecology [A. G. J. v. d. Z., H. B.], the Division of Medical Oncology, Department of Internal Medicine [S. d. J., J. G. Z., P. H. B. W., E. G. E. d. V.], and Department of Pathology [H.H., A.G.], University Hospital, Oostersingel 59, 9713 EZ Groningen, The Netherlands

P-glycoprotein (P-gp) expression and DNA topoisomerase (Topo) II are important variables in multidrug resistant tumor cell lines. The aim of this study was to evaluate P-gp expression and Topo I and II activity in benign and malignant epithelial ovarian tumors. P-gp expression was analyzed immunohistochemically in cryostat sections of fresh tumor specimens. In the same specimens Topo I and II activity were measured by, respectively, relaxation of supercoiled plasmid pBR322 DNA and decatenation of kinetoplast DNA. P-gp expression (range, 5–100% positive staining cells) was found in 3 of 6 cystadenomas, 0 of 2 borderline tumors, 15 of 21 untreated ovarian cancers, and 8 of 13 platinum/cyclophosphamide treated ovarian cancers. Median Topo I and II activity were elevated in malignant ovarian tumors compared to benign and borderline tumors. No difference was found between median Topo I activity in untreated ovarian cancer and platinum/cyclophosphamide treated ovarian cancer. High Topo II activity (8 x 10² units/mg protein) was more frequent in untreated compared to platinum/cyclophosphamide treated samples. Respectively, 8- and 16-fold differences in Topo I and II activity were found in the malignant tumors. Topo II activity in malignant tumors correlated with Topo I activity (r = 0.36, P < 0.05) and the tumor volume index (r = 0.35, P < 0.05). However, this last weak correlation cannot explain the 16-fold differences in Topo II activity in malignant tumors. Mitotic index and P-gp expression did not correlate with Topo I or II activity. A large variability in P-gp expression and Topo I and II activity was observed in patients with ovarian cancer.

¹ This study was supported by Grants GUKC 90-18 and GUKC 91-12 from the Dutch Cancer Society.

² To whom requests for reprints should be addressed.

Received 4/ 8/91. Accepted 8/19/91.

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