MDM-2 MESSENGER-RNA EXPRESSION IS ASSOCIATED WITH SURVIVAL IN OVARIAN-CANCER

Expression of mdm-2 mRNA was measured in 90 ovarian-cancer tissue spec imens using the SI nuclease assay, to investigate a possible associati on between MDM2 expression and prognosis. mdm-2 mRNA expression was an independent prognostic factor for patients with primary ovarian cance r, FIGO (International Federation of Gynecology and Obstetrics) stages III and IV (n = 57), who all received chemotherapy with carboplatin o r cisplatin and cyclophosphamide. Median survival time for patients (F IGO stages III and IV) with no detectable expression of mdm-2 mRNA (n = 14) was 171 days, as compared with 839 days for patients (n = 43) wi th detectable mdm-2 mRNA (p = 0.0194; log-rank test), However, no asso ciation between mdm-2 mRNA expression and survival was observed for pa tients with FIGO stages I and II who did not receive chemotherapy. mdm -2 expression was not associated with FIGO stage, residual disease, hi stologic grade and type. Our results suggest that mdm-2, which is know n to disrupt p53 function, sensitizes ovarian-cancer cells to cisplati n/cyclophosphamide, possibly by inhibition of p53-mediated GI cell-cyc le arrest and p53-stimulated nucleotide-excision repair, (C) 1997 Wile y-Liss, Inc.