Tanner B, Hengstler J G, Laubscher S, Meinert R, Oesch F, Weikel W, Knapstein P G, Becker R
Department of Gynecology and Obstetrics, University of Mainz, Germany.
Int J Cancer. 1997 Aug 22;74(4):438-42. doi: 10.1002/(sici)1097-0215(19970822)74:4<438::aid-ijc13>3.0.co;2-5.
Expression of mdm-2 mRNA was measured in 90 ovarian-cancer tissue specimens using the S1 nuclease assay, to investigate a possible association between MDM2 expression and prognosis. mdm-2 mRNA expression was an independent prognostic factor for patients with primary ovarian cancer, FIGO (International Federation of Gynecology and Obstetrics) stages III and IV (n = 57), who all received chemotherapy with carboplatin or cisplatin and cyclophosphamide. Median survival time for patients (FIGO 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) with detectable mdm-2 mRNA (p = 0.0194; log-rank test). However, no association between mdm-2 mRNA expression and survival was observed for patients with FIGO stages I and II who did not receive chemotherapy. mdm-2 expression was not associated with FIGO stage, residual disease, histologic grade and type. Our results suggest that mdm-2, which is known to disrupt p53 function, sensitizes ovarian-cancer cells to cisplatin/cyclophosphamide, possibly by inhibition of p53-mediated G1 cell-cycle arrest and p53-stimulated nucleotide-excision repair.
采用S1核酸酶分析法检测了90份卵巢癌组织标本中mdm-2 mRNA的表达,以研究MDM2表达与预后之间的可能关联。mdm-2 mRNA表达是原发性卵巢癌FIGO(国际妇产科联盟)III期和IV期患者(n = 57)的独立预后因素,这些患者均接受了卡铂或顺铂及环磷酰胺化疗。mdm-2 mRNA无表达(n = 14)的患者(FIGO III期和IV期)的中位生存时间为171天,而mdm-2 mRNA有表达的患者(n = 43)为839天(p = 0.0194;对数秩检验)。然而,对于未接受化疗的FIGO I期和II期患者,未观察到mdm-2 mRNA表达与生存之间的关联。mdm-2表达与FIGO分期、残留病灶、组织学分级和类型无关。我们的结果表明,已知可破坏p53功能的mdm-2使卵巢癌细胞对顺铂/环磷酰胺敏感,可能是通过抑制p53介导的G1期细胞周期阻滞和p53刺激的核苷酸切除修复。