Yang Lian-yue, Lu Wei-qun, Huang Geng-wen, Wang Wei
Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China.
BMC Cancer. 2006 May 2;6:110. doi: 10.1186/1471-2407-6-110.
Angiogenesis is one of the mechanisms most critical to the postoperative recurrence and metastasis of hepatocellular carcinoma (HCC). Thus, finding the molecular markers associated with angiogenesis may help identify patients at increased risk for recurrence and metastasis of HCC. This study was designed to investigate whether CD105 or CD34 could serve as a valid prognostic marker in patients with HCC by determining if there is a correlation between CD105 or CD34 expression and postoperative recurrence or metastasis.
Immunohistochemical staining for the CD105, CD34 and vascular endothelial growth factor (VEGF) antibodies was performed in 113 HCC tissue specimens containing paracarcinomatous tissue and in 14 normal liver tissue specimens. The quantitation of microvessels identified by anti-CD105 and anti-CD34 monoclonal antibodies and the semiquantitation of VEGF expression identified by anti-VEGF monoclonal antibody were analyzed in conjunction with the clinicopathological characteristics of the HCC and any available follow-up information about the patients from whom the specimens were obtained.
CD105 was not expressed in the vascular endothelial cells of any normal liver tissue or paracarcinomatous liver tissue but was expressed in the vascular endothelial cells of all HCC tissue. In contrast, CD34 was expressed in the vascular endothelial cells of normal liver tissue, paracarcinomatous tissue, and HCC tissue in the following proportions of specimens: 86.7%, 93.8%, and 100%, respectively. The microvascular densities (MVDs) of HCC determined by using an anti-CD105 mAb (CD105-MVD) and an anti-CD34 mAb (CD34-MVD), were 71.7 +/- 8.3 (SD) and 106.3 +/- 10.4 (SD), respectively. There was a significant correlation between CD105-MVD and CD34-MVD (r = 0.248, P = 0.021). Although CD34-MVD was significantly correlated with VEGF expression (r = 0.243, P = 0.024), CD105-MVD was more closely correlated (r = 0.300, P= 0.005). The correlation between microscopic venous invasion and CD105-MVD, but not CD34-MVD, was also statistically significant (r = 0.254, P = 0.018). Univariate analysis showed that CD105-MVD was significantly correlated with the 2-year overall survival rate (P = 0.014); CD34-MVD was not (P = 0.601). Multivariate analysis confirmed that CD105-MVD was an independent prognostic factor and that CD34-MVD was not.
The anti-CD105 mAb is an ideal instrument to quantify new microvessels in HCC as compared with anti-CD34 mAb. CD105-MVD as compared with CD34-MVD is relevant a significant and independent prognostic indicator for recurrence and metastasis in HCC patients.
血管生成是肝细胞癌（HCC）术后复发和转移的最关键机制之一。因此，寻找与血管生成相关的分子标志物可能有助于识别HCC复发和转移风险增加的患者。本研究旨在通过确定CD105或CD34表达与术后复发或转移之间是否存在相关性，来研究CD105或CD34能否作为HCC患者有效的预后标志物。
对113例含有癌旁组织的HCC组织标本和14例正常肝组织标本进行CD105、CD34和血管内皮生长因子（VEGF）抗体的免疫组织化学染色。结合HCC的临床病理特征以及从标本获取患者的任何可用随访信息，分析抗CD105和抗CD34单克隆抗体识别的微血管定量以及抗VEGF单克隆抗体识别的VEGF表达半定量。
CD105在任何正常肝组织或癌旁肝组织的血管内皮细胞中均不表达，但在所有HCC组织的血管内皮细胞中均有表达。相比之下，CD3分别在正常肝组织、癌旁组织和HCC组织的血管内皮细胞中表达，标本比例如下：86.7%、93.8%和100%。使用抗CD105单克隆抗体（CD105-MVD）和抗CD34单克隆抗体（CD34-MVD）测定的HCC微血管密度（MVD）分别为71.7±8.3（标准差）和106.3±10.4（标准差）。CD105-MVD与CD34-MVD之间存在显著相关性（r = 0.248，P = 0.021）。虽然CD34-MVD与VEGF表达显著相关（r = 0.243，P = 0.024），但CD105-MVD相关性更强（r = 0.300，P = 0.005）。显微镜下静脉侵犯与CD105-MVD之间的相关性也具有统计学意义（r = 0.254，P = 0.018），而与CD34-MVD无关。单因素分析显示，CD105-MVD与2年总生存率显著相关（P = 0.014）；CD34-MVD则不然（P = 0.601）。多因素分析证实，CD105-MVD是独立的预后因素，而CD34-MVD不是。
与抗CD34单克隆抗体相比，抗CD105单克隆抗体是定量HCC中新微血管的理想工具。与CD34-MVD相比，CD105-MVD是HCC患者复发和转移的重要且独立的预后指标。
