Kim Y B, Park Y N, Park C
Department of Pathology, Ajou University School of Medicine, Suwon, Korea.
Histopathology. 2001 Feb;38(2):160-6. doi: 10.1046/j.1365-2559.2001.01064.x.
Transcatheter arterial embolization induces extensive ischaemic necrosis or hypoxia via the obstruction of the hepatic artery in hepatocellular carcinoma (HCC). Ischaemia is strongly correlated with an increased expression of angiogenic factor and stimulates an increase in angiogenesis, including endothelial cell proliferation. The aim of this study was to evaluate whether ischaemic necrosis induced by transcatheter arterial embolization could increase the proliferative activities of intratumoral endothelial cells or tumour cells in the residual HCC.
Using a double immunohistochemical technique (Ki67 antibody to determine the proliferative activity and CD34 antibody to highlight the intratumoral endothelial cells), we performed immunohistochemical staining for 24 HCCs treated by transcatheter arterial embolization. Seven HCCs without any preoperative transcatheter arterial embolization and nine cirrhosis cases were also studied as the control cases. The residual tumour was then divided into five areas at 0.5 mm intervals, according to the distance from the necrotic margin induced by embolization. The Ki67 labelling indices of the intratumoral endothelial cells and tumour cells were counted in each area. The correlation between the indices and the corresponding distance from the ischaemic necrosis was analysed. The Ki67 labelling index of intratumoral vascular endothelial cells in the area less than 0.5 mm from the necrotic margin (area 1) was 10.60 +/- 3.64% (mean +/- SD), which was twofold greater than those of the other areas more than 0.5 mm from the margin (areas 2--5) and those of the control HCCs without preoperative transcatheter arterial embolization. In addition, the proliferation labelling index of the tumour cells was 35.77 +/- 11.45% (mean +/- SD) in area 1. This was higher than those of areas 2--5 and control HCCs without preoperative transcatheter arterial embolization. There was a positive correlation between the proliferation of both endothelial and tumour cells and ischaemic necrosis (P < 0.05).
Our study suggests that the proliferative activity of intratumoral endothelial cells and tumour cells is increased by ischaemic necrosis induced by transcatheter arterial embolization, and its effect is maximal in the area adjacent to the necrosis (less than 0.5 mm from the necrotic margin).
经导管动脉栓塞术通过阻塞肝细胞癌（HCC）的肝动脉诱导广泛的缺血性坏死或缺氧。缺血与血管生成因子表达增加密切相关，并刺激血管生成增加，包括内皮细胞增殖。本研究的目的是评估经导管动脉栓塞术诱导的缺血性坏死是否会增加残余HCC中肿瘤内内皮细胞或肿瘤细胞的增殖活性。
采用双重免疫组织化学技术（用Ki67抗体确定增殖活性，用CD34抗体突出肿瘤内内皮细胞），对24例行经导管动脉栓塞术治疗的HCC进行免疫组织化学染色。7例未行任何术前经导管动脉栓塞术的HCC和9例肝硬化病例也作为对照病例进行研究。然后根据距栓塞诱导的坏死边缘的距离，将残余肿瘤以0.5毫米的间隔分为五个区域。在每个区域计数肿瘤内内皮细胞和肿瘤细胞的Ki67标记指数。分析指数与距缺血性坏死相应距离之间的相关性。距坏死边缘小于0.5毫米的区域（区域1）内肿瘤血管内皮细胞的Ki67标记指数为10.60±3.64%（平均值±标准差），是距边缘大于0.5毫米的其他区域（区域2-5）以及未行术前经导管动脉栓塞术的对照HCC的两倍。此外，区域1内肿瘤细胞的增殖标记指数为35.77±11.45%（平均值±标准差）。这高于区域2-5以及未行术前经导管动脉栓塞术的对照HCC。内皮细胞和肿瘤细胞的增殖与缺血性坏死之间存在正相关（P<0.05）。
我们的研究表明，经导管动脉栓塞术诱导的缺血性坏死会增加肿瘤内内皮细胞和肿瘤细胞的增殖活性，且在与坏死相邻的区域（距坏死边缘小于0.5毫米）效果最大。
