VEGF、ANG-1、ANG-2、TSP-1的表达与胆管细胞性肝癌血管生成和侵润转移的关系

目的：研究血管内皮生长因子（VEGF）、血管生成素-1（ANG-1）、血管生成素-2（ANG-2）、血小板反应蛋白-1（TSP-1）的表达与胆管细胞性肝癌(CCC)血管生成和侵润转移的关系。方法： 对33例手术切除的CCC标本进行CD34、VEGF、 ANG-1、 ANG-2 和TSP-1的免疫组化染色，研究VEGF、ANG-1、ANG-2、TSP-1的表达与胆管细胞性肝癌血管生成和肿瘤门静脉侵犯、肝内转移、淋巴结转移以及肿瘤分化水平之间的关系。 结果： 本组CCC的微血管密度（MVD）为(87.2±52.6)/mm2，VEGF、ANG-1、ANG-2 和TSP-1的阳性率分别为75.6%、36.0%、57.6%和45.5%。VEGF和ANG-2的阳性表达与高MVD相关，TSP-1则与MVD负相关（P<0.01,P<0.05,P<0.01）。阳性TSP-1与肝内转移正相关（46.7% vs 5.6%，P<0.05）。结论： CCC瘤内的血管新生活跃，VEGF和ANG-2的阳性表达与CCC血管生成正相关，TSP-1则与其负相关，TSP-1的阳性表达还与肝内转移相关，VEGF、ANG-1、ANG-2的表达与肿瘤的侵润转移未见显著相关。

Expressions of VEGF,ANG-1,ANG-2 and TSP-1 in cholangiocellular carcinoma and relationship with tumor angiogenesis,differentiation,invasion and metastasis

AIM: To investigate the angiogenesis status,the expression of vascular endothelial growth factor (VEGF),angiopoietin-1 (ANG-1),angiopoietin-2 (ANG-2),thrombospondin-1 (TSP-1) in cholangiocellular carcinoma (CCC) and relationship with tumor angiogenesis,differentiation,invasion and metastasis. METHODS: 33 specimen of surgically resected CCC were investigated.Immunohistochemical staining of CD34,VEGF,ANG-1,ANG-2 and TSP-1 was carried out. RESULTS: The mean MVD was (87.2±52.6)/mm2.VEGF positive expression was found in 75.6% cases;ANG-1 positive expression was observed in 36% cases;ANG-2 positive was detected in 57.6% cases and 45.5% cases exhibited positive TSP-1 expression.VEGF and ANG-2 expressions were found to be associated with significant higher level of MVD (P<0.01 and P<0.05,respectively).TSP-1 expression was found to be associated with significant low level of MVD (P<0.01).Positive TSP-1 expression was also found to be associated with higher level of intrahepatic metastasis (46.7% vs 5.6%,P<0.05). CONCLUSION: Considerable angiogenesis compared to other solid tumors can be observed in CCC.VEGF and ANG-2 might play a proangiogenic role and TSP-1 may play an inhibitory role.Although TSP-1 may increase the intrahepatic metastasis of CCC,neither MVD levels nor the expression of VEGF,ANG-1,or ANG-2 is associated with tumor differentiation,invasion and metastasis.