title: Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer.
abstract: This retrospective study of ovarian cancer aimed to elucidate whether expression of apoptosis-related proteins, bcl-2, p53 or MDM-2, is associated with resistance to chemotherapy, especially cisplatin (CDDP) based chemotherapy. Expression of bcl-2, p53 and MDM-2 was assessed by immunohistochemical staining of tumour tissues collected at initial surgery prior to treatment with CDDP-based chemotherapy. Among 66 patients with advanced ovarian cancer with measurable tumour following surgery and evaluable for response to chemotherapy, 42, 45 and 56% were positive for bcl-2, p53 and MDM-2, respectively. Significantly fewer tumours of patients who had a complete response to chemotherapy (CR) showed positivity for bcl-2 (2/20) than for p53 (6/20) and MDM-2 (8/20, P < 0.001). There was an inverse correlation between bcl-2 staining and initial response to chemotherapy, especially in serous and endometrial adenocarcinomas. In patients with stage III-IV, serous or endometrioid adenocarcinomas, significantly poorer survival was seen for those with bcl-2 positive tumours than those with negative bcl-2 staining (P = 0.0064). p53 and MDM-2 were not correlated with initial response to chemotherapy. Multivariate analysis revealed that bcl-2, residual tumour size and histology were significant independent prognostic factors. These results suggest that bcl-2 can be a possible predictor of response to chemotherapy and prognosis in patients with advanced ovarian carcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mano
authors.forename: Y
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Kita
authors.forename: J
authors.initials: J
authors.lastname: Hirata
authors.forename: T
authors.initials: T
authors.lastname: Tode
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: I
authors.initials: I
authors.lastname: Nagata
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002945:Cisplatin