肝细胞癌中血管内皮生长因子及其受体的表达与意义

Expressions and significance of VEGF and VEGF receptors in hepatocellular carcinoma

目的 :探讨血管内皮生长因子(VEGF)和血管内皮生长因子受体 (VEGFRs)在肝细胞癌 (HCC)肿瘤血管生成中的调节作用。方法 :采用免疫组化法检测 3 9例 (男 3 4例 ,女 5例 )共 41个经手术病理证实的HCC病灶VEGF、Flt 1和KDR/Flk 1的蛋白表达。观察病灶肿瘤大小、包膜、子灶、门静脉癌栓、肝门淋巴结转移和肝硬化等。记录HCC患者的临床资料 ,如年龄、HBsAg、HBV和AFP情况。手术结果记录病灶大小、数目、肝硬化和包膜情况。病理结果记录病理分级、肝硬化等情况。结果 :在转移高危组、包膜欠完整和 (或 )无包膜组、小肝癌组中VEGF表达阳性率均高于转移低危组、包膜完整组和大肝癌组 ,差异有统计学意义 ,P <0 0 5。而VEGF的表达与Ed mondson分级、HBV、HBsAg、AFP水平以及肝硬化之间差异均无统计学意义 ,P >0 0 5。KDR/Flk 1表达阳性病灶 2 9个 ,阳性率为 70 73 %( 2 9/4 1) ;KDR/Flk 1在转移高危组、包膜欠完整和 (或 )无包膜组、小肝癌组中表达的阳性率也均高于转移低危组、包膜完整组和大肝癌组 ,差异有统计学意义 ,P <0 0 5。KDR/Flk 1蛋白的表达亦与Edmondson分级、HBV、HBsAg、AFP水平、肝硬化之间差异无统计学意义 ,P >0 0 5。Flt 1阳性病灶 2 8个 ,阳性率为 68 2 9% ( 2 8/4 1) ;Flt

OBJECTIVE:To study the expression and modulation of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) in the angiogenesis of hepatocellular carcinoma (HCC). METHODS:Thirty nine cases (41 lesions) of HCC were proved surgically. The clinicopathological characteristics including the size, capsule, the edge of lesions, intrahepatic daughter foci, tumor-emboli in portal veins, lymphaden metastasis and hepatic cirrhosis were analysed. The details about the size, capsule and the edge of lesions were recorded after resection. The grades of differentiation and hepatic cirrhosis were recorded in pathology. The expressions of VEGF and VEGFRs were detected with immunohistochemical SP method. The clinical and histopathological characteristics of HCC were compared with the immunohistochemical results of VEGF, Flt-1 and KDR/Flk-1. RESULTS: The diameter was equal to or smaller than 5 cm in 22 lesions (22/41, 53.66%), the diameter was larger than 5 cm in 19 lesions (19/41, 46.34%); pseudocapsula were found in 12 lesions (12/41, 29.27%), incomplete pseudocapsula or non-pseudocapsula were found in 29 lesions (29/41, 70.73%). There were 11 lesions (11/41, 26.83%) in high potential invasion and metastasis (intrahepatic daughter foci, tumor-emboli in portal veins, lymphaden metastasis), 30 lesions (30/41, 73.17%) in the low potential invasion and metastasis group. Thirty-two lesions (32/41, 78.05%) were accompanied by hepatic cirrhosis and the others (9/41, 21.95%) were not. There were significantly high expressions of VEGF and KDR/Flk-1 in the group of high potential invasion and metastasis, in the group of HCC with incomplete pseudocapsula or without pseudocapsula, and in the group of lesions whose diameter equal to or smaller than 5 cm. The expressions of Flt-1 had no significance in all the groups mentioned above. It showed that VEGF expression correlated with KDR/Flk-1, but KDR/Flk-1 expressions did not correlate with Flt-1.CONCLUSIONS:VEGF and KDR/Flk-1 play a potentially important role in the angiogenesis, growth and metastasis of HCC.