Mano Y, Kikuchi Y, Yamamoto K, Kita T, Hirata J, Tode T, Ishii K, Nagata I
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan.
Eur J Cancer. 1999 Aug;35(8):1214-9. doi: 10.1016/s0959-8049(99)00124-0.
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.
这项针对卵巢癌的回顾性研究旨在阐明凋亡相关蛋白bcl-2、p53或MDM-2的表达是否与化疗耐药相关,尤其是与基于顺铂(CDDP)的化疗耐药相关。通过对接受基于CDDP化疗前初次手术时采集的肿瘤组织进行免疫组织化学染色,评估bcl-2、p53和MDM-2的表达。在66例术后有可测量肿瘤且可评估化疗反应的晚期卵巢癌患者中,bcl-2、p53和MDM-2阳性的患者分别占42%、45%和56%。化疗完全缓解(CR)的患者中,bcl-2阳性的肿瘤(2/20)显著少于p53阳性的肿瘤(6/20)和MDM-2阳性的肿瘤(8/20,P<0.001)。bcl-2染色与化疗初始反应呈负相关,尤其是在浆液性和子宫内膜腺癌中。在Ⅲ-Ⅳ期浆液性或子宫内膜样腺癌患者中,bcl-2阳性肿瘤患者的生存期明显短于bcl-2染色阴性的患者(P = 0.0064)。p53和MDM-2与化疗初始反应无关。多因素分析显示,bcl-2、残余肿瘤大小和组织学是显著的独立预后因素。这些结果表明,bcl-2可能是晚期卵巢癌患者化疗反应和预后的一个可能预测指标。