MVD-CD105和MVD-CD34在肝细胞肝癌中的表达及其与肝移植预后的关系

Tumor Microvascular Density Detected by Anti-CD105 and Anti-CD34 in Hepatocellular Carcinoma Patients and Its Predictive Value of Tumor Recurrence after Liver Transplantation

目的探讨抗CD105、CD34抗体标记的肿瘤微血管密度(microvascular density,MVD)在肝细胞肝癌(hepatocellular carcinoma,HCC)中的表达及其判断HCC肝移植(liver transplantation,LT)术后肿瘤复发的临床应用价值。方法收集2001年1月至2006年12月期间获得随访资料的112例HCC肝移植患者为研究对象,应用免疫组织化学方法检测112例(其中伴有癌旁组织为100例)HCC肝移植患者肿瘤组织中微血管CD105、CD34的表达,分析其与肝移植术后复发的相关性并与临床病理指标进行比较。结果 CD34主要表达于HCC的肿瘤区域,显示瘤内成熟肿瘤血管,而CD105主要表达于紧邻肿瘤的癌旁区域,能够显示癌旁活性新生血管;pTNM分期、肿瘤直径及甲胎蛋白(AFP)值仅在单因素分析中对预测肝移植复发有统计学意义(P<0.05),癌旁MVD-CD105和门静脉癌栓(portal veintumor thrombus,PVTT)在单因素及多因素分析中均显示对预测肝移植复发有统计学意义(P<0.05),并且癌旁MVD-CD105与门静脉癌栓(rs=0.257,P=0.010)、pTNM分期(rs=0.350,P=0.000)、AFP(rs=0.208,P=0.038)具有相关性。结论抗CD105抗体可作为标记肝癌内活性新生血管的理想标记物,MVD-CD105在HCC癌旁组织中的表达可作为HCC肝移植术后预测复发的一项独立指标,有前景成为辅助HCC肝移植术后进一步治疗的标记物。

Objective To investigate the clinical significance of tumor microvascular density(MVD) detected by anti-CD105 and anti-CD34 as a predictor of recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT).Methods One hundred and twelve(100 with adjacent nontumorous area) patients with HCC who underwent LT between Jan.2001 and Dec.2006 were included in this retrospective study.Paraffin blocks of tumor tissue and adjacent nontumorous tissue were used for immunohistochemical study.MVD of HCC was evaluated by anti-CD105 monoclonal antibody and anti-CD34 monoclonal antibody.Results The immunohistochemich staining showed CD34 strongly positive expressed in the tumor area with tumor mature vasculature,and CD105 strongly positive expressed in adjacent nontumorous area with tumor newly formed vessels.Univariate analysis using chi-square test showed portal vein tumor thrombus(PVTT),pTNM stage,MVD-CD105 expression in adjacent nontumorous area,tumor size and serum AFP level were significantly associated with HCC recurrence after LT(P<0.05).Multivariate analysis by Cox’s regression model showed MVD-CD105 expression in adjacent nontumorous area and PVTT still remained significant correlation with recurrence of HCC after LT(P<0.05), and MVD-CD105 in adjacent nontumorous area was significantly correlated with PVTT(rs=0.257,P=0.01),pTNM stage(rs=0.350,P=0.000),as well as serum AFP level(rs=0.208,P=0.038).Conclusion The anti-CD105 mAb is an ideal tool to quantify new microvessels in HCC.MVD-CD105 expression in adjacent nontumorous area may be used as an additional factor for the identification of patients at risk for post-transplant recurrence.