【摘要】 目的研究多药耐药相关蛋白2、3(MRP2、MRP3)表达与原发性肝细胞癌(HCC)合并门静脉癌栓患者术后辅助化疗疗效的相关性。方法收集2001年1月至2005年12月术后接受化疗的29例HCC合并门静脉癌栓患者的石蜡标本,构建组织芯片。采用免疫组织化学染色技术检测MRP2、MRP3的表达情况。将蛋白表达强度(++)以上设为耐药组,其余为非耐药组,结合临床资料进行生存分析。结果 MRP2、MRP3阳性表达率分别为86.21%(25/29)和62.07%(18/29)。依据MRP2表达情况,耐药组19例和非耐药组10例进行生存分析显示,总体生存期(P=0.010)及无瘤生存期(P=0.039)差异有统计学意义。依据MRP3表达情况,耐药组16例和非耐药组13例比较,仅无瘤生存期差异有统计学意义(P=0.043)。多因素Cox回归分析显示,MRP2(P=0.009,HR=4.897,95%CI=1.475~16.261)、MRP3(P=0.002,HR=5.515,95%CI=1.861~16.341)表达情况为无瘤生存的独立影响因子。结论 MRP2、MRP3的强表达是导致肝癌耐药及化疗效果欠佳的原因之一。MRP2、MRP3有可能作为原发性肝癌患者临床筛选化疗方案的指标。更多还原

【Abstract】 Objective To investigate the expression of multidrug resistance- associated proteins(MRP2, MRP3) and their correlation to chemotherapeutic efficacy in hepatocellular carcinoma(HCC) with tumor thrombi in major portal vein. Methods Twenty-nine HCC patients with tumor thrombi in major portal vein following hepatectomy, thrombectomy and postoperative adjuvantchemotherapy were enrolled in this study. Specimens embedded in paraffin were collected for the construction of tissue microarrays. MRP2 and MRP3 were visualized by immunohistochemical staining. The patients were divided into chemotherapy sensitive and resistant groups according to the staining grade. The intensity ≥(++) were considered resistant to chemotherapy. Survival time was compared between the two groups and prognostic factors were identified using Cox proportional hazards model. Results The positive rate of MRP2 and MRP3 was 86.21%, 62.07%, respectively. Tumor-free survival time and overall survival time were significantly different between the two groups according to the staining grade of MRP2(P=0.039, 0.010, respectively). Only tumor-free survival time was significantly different according to the staining grade of MRP3(P=0.043). Multivariate analysis revealed that the expression grade of MRP2 and MRP3 was independent prognostic factor for tumor-free survival time(P=0.009, 0.002, respectively). Conculsion In HCC patients with tumor thrombi in major portal vein, the overexpression of MRP2, MRP3 is one of the major reasons for resistance to chemotherapy. Detection of MRP2 and MRP3 will be helpful in chemotherapy decision making.更多还原