Morinaga S, Imada T, Shimizu A, Akaike M, Sugimasa Y, Takemiya S, Takanashi Y
First Department of Surgery, Yokohama City University, School of Medicine 3-9 Fukuura, Kanazawaku, Yokohama 236-0004, Japan.
Hepatogastroenterology. 2001 Jan-Feb;48(37):224-8.
BACKGROUND/AIMS: Angiogenesis has been known to be associated with tumor development. In this study, neovascularization in small hepatocellular carcinoma was investigated by evaluation of intratumoral arteriole counts, using alpha smooth muscle actin antibody immunohistochemistry.
Surgical specimens from 38 patients with small hepatocellular carcinoma were immunostained for alpha smooth muscle actin and proliferating cell nuclear antigen. The correlation between intratumoral arteriole density and clinicopathological factors including angiographic findings, proliferative activity, and patient prognosis were analyzed.
Significant difference in intratumoral arteriole density were observed between well-differentiated hepatocellular carcinoma and poorly differentiated hepatocellular carcinoma (P = 0.004) or moderately differentiated hepatocellular carcinoma and poorly differentiated hepatocellular carcinoma (P = 0.011). The mean intratumoral arteriole count in the tumors showing angiographic hypervascularity was significantly higher than that in the tumors without angiographic hypervascularity (P = 0.011). A significant and positive correlation was found between proliferating cell nuclear antigen labeling index and intratumoral arteriole density (r = 0.5232, P = 0.001). A high intratumoral arteriole density in tumor was significantly correlated with shorter patients survival (P = 0.018). Cox's multivariate regression analysis showed that the intratumoral arteriole density was independent prognostic factors (P = 0.0306).
Intratumoral arteriole density was found to be significantly associated with histological grade, proliferative activity, and patient survival. It also reflected the angiographic findings. Alpha smooth muscle actin antibody immunohistochemistry would provide a simple and biologically significant method which is usable to screen neovascularization and arterial blood supply in hepatocellular carcinoma, and may have predicting utility for patients outcome. This technique is applicable to routine paraffin sections, and may be useful as an adjunct to surgical pathology of hepatocellular carcinoma.
背景/目的：已知血管生成与肿瘤发展相关。在本研究中，通过使用α平滑肌肌动蛋白抗体免疫组织化学评估肿瘤内小动脉计数，对小肝细胞癌中的新生血管形成进行了研究。
对38例小肝细胞癌患者的手术标本进行α平滑肌肌动蛋白和增殖细胞核抗原免疫染色。分析肿瘤内小动脉密度与包括血管造影结果、增殖活性和患者预后在内的临床病理因素之间的相关性。
在高分化肝细胞癌与低分化肝细胞癌（P = 0.004）或中分化肝细胞癌与低分化肝细胞癌之间观察到肿瘤内小动脉密度存在显著差异（P = 0.011）。显示血管造影高血供的肿瘤中的平均肿瘤内小动脉计数显著高于无血管造影高血供的肿瘤（P = 0.011）。增殖细胞核抗原标记指数与肿瘤内小动脉密度之间存在显著正相关（r = 0.5232，P = 0.001）。肿瘤内高小动脉密度与患者较短生存期显著相关（P = 0.018）。Cox多因素回归分析表明肿瘤内小动脉密度是独立的预后因素（P = 0.0306）。
发现肿瘤内小动脉密度与组织学分级、增殖活性和患者生存显著相关。它还反映了血管造影结果。α平滑肌肌动蛋白抗体免疫组织化学将提供一种简单且具有生物学意义的方法，可用于筛查肝细胞癌中的新生血管形成和动脉血供，并且可能对患者预后具有预测作用。该技术适用于常规石蜡切片，可能作为肝细胞癌手术病理学的辅助手段有用。
