P-糖蛋白表达与原发性肝癌合并门静脉癌栓患者术后辅助化疗效果的相关性研究

Correlation between the expression of P-gp and efficacy of chemotherapy postoperation in hepatocellular carcinoma patients with tumor thrombi in major portal vein

目的研究P-糖蛋白(P-gp)表达与原发性肝细胞癌合并门静脉癌栓患者表达情况与临床化疗效果之间的关系。方法收集术后接受化疗的29例原发性肝细胞癌合并门静脉癌栓患者的石蜡块,构建组织芯片。采用免疫组化染色技术,检测P-gp蛋白的表达情况。根据P-gp蛋白表达强弱分为耐药组和非耐药组,进行生存分析。结果 P-gp蛋白表达的阳性率为75.86%(22/29)。中位无瘤生存期在耐药组(20例)与非耐药组(9例)间有显著差别。多因素Cox回归分析显示P-gp表达情况为无瘤生存期的独立影响因子。结论 P-gp的强表达是导致肝癌耐药、化疗效果欠佳的原因之一,P-gp有可能作为临床筛选化疗患者的指标。

Objective To investigate the expression of P-glycoprotein （P-gp） and its correlation to chemotherapeutic efficacy in hepatoeellular carcinoma （HCC） with tumor thrombi in major portal vein. Methods Twenty-nine patients of HCC with tumor thrombi in major portal vein following hepatectomy and thrombectomy were enrolled in this study, all the patients received immunochemotherapy postperatively. Specimens embedded in paraffin were collected for the construction of tissue microarrays. P-gp protein were visualized by immunohistochemical staining using Monoclonal antibodies JSB-1. 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 P-gp was 75.86% （22/29）. Medium tumor-free survival time showed significant differences between two groups. Multivariate analysis revealed that the expression grade of P-gp was independent prognostic factor for tumor-free survival time. Conclusion In HCC with tumor thrombi in major portal vein, the overexpression of P-gp is one of the major reason for resistance to chemotherapy, detection of which will be helpful in chemotherapy decision making.