O6-methylguanine-DNA methyltransferase in ovarian malignancy and its correlation with postoperative response to chemotherapy.

O6-Methylguanine-DNA methyltransferase (MGMT) in human neoplastic tissues has been associated with tumor resistance to alkylating agents. The purposes of this study are to assay MGMT activity in ovarian cancers and to correlate MGMT titers with chemotherapy response to cisplatin and cyclophosphamide in patients with ovarian cancer. MGMT levels were determined by a biochemical assay of tumor tissues from 20 patients with ovarian malignancy. The clinical stages of the patients studied were 4 in Stage I, 2 in Stage II, 12 in Stage III, and 2 in Stage IV. The mean MGMT activity was 34 +/- 9 fmole methyls transferred/mg protein. Among 13 patients with tumor MGMT levels more than 10 fmole/mg protein, 10 (77%) of them were resistant to postoperative combination chemotherapy. In the remaining 7 patients with low MGMT titer of less than 10 fmole/mg protein, a majority (71%) had a complete response (P < 0.10). These preliminary results indicate that ovarian cancer has detectable MGMT activity, and this activity is possibly correlated with treatment failure to a postoperative cisplatin regimen.