Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan; Department of Pathology, Tohoku University Hospital, Sendai 980-8574, Japan.
Department of Pathology, Tohoku University Hospital, Sendai 980-8574, Japan.
Hum Pathol. 2014 Mar;45(3):589-97. doi: 10.1016/j.humpath.2013.10.028. Epub 2013 Nov 6.
Vasohibin 1, an endothelium-derived negative feedback regulator of angiogenesis, is induced by fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor A (VEGF-A). In this study, we retrospectively evaluated immunoreactivity of FGF-2 and VEGF-A as well as microvessel density (MVD) determined by expression of vasohibin 1 and CD34 (MVD-CD34) and correlated the findings with clinical outcomes of 181 patients with hepatocellular carcinoma (HCC). Double immunostaining of an endothelial marker CD34 and vasohibin 1 with Ki-67 was also performed to assess angiogenic activity of endothelial cells in HCC. The ratio of Ki-67-positive endothelial cells in vasohibin 1-positive vessels (22%) was significantly higher than that of CD34-positive vessels (9%, P < .001), suggesting the correlation between vasohibin 1 and neovascularization in endothelial cells of HCC. MVD-CD34 decreased, but the ratio of MVD determined by expression of vasohibin 1 to MVD-CD34 (vasohibin 1/CD34) increased significantly according to histologic grade. Vasohibin 1 was significantly correlated with the status of FGF-2 (P = .007) but not with that of VEGF-A (P = .055). The 10-year overall survival and the 2-year disease-free survival rates of the low vasohibin 1/CD34 group (vasohibin 1/CD34 ≤0.459) were significantly higher than those of the high vasohibin 1/CD34 group (vasohibin 1/CD34 >0.459) (survival, 48% versus 38% and 52% versus 35%; P < .001 and P < .05, respectively). In addition, vasohibin 1/CD34 in HCC patients was an independent marker of poor prognosis, as determined by multivariate analysis (risk ratio, 1.973; 95% confidence interval, 1.049-3.711; P = .035). Vasohibin 1/CD34 could identify the proliferative vessels and could be a useful biomarker for predicting the clinical outcome of HCC patients.
血管抑素 1 是一种内皮衍生的血管生成负反馈调节剂，由成纤维细胞生长因子 2（FGF-2）和血管内皮生长因子 A（VEGF-A）诱导。在这项研究中，我们回顾性评估了 FGF-2 和 VEGF-A 的免疫反应性以及微血管密度（MVD），通过血管抑素 1 和 CD34 的表达来确定（MVD-CD34），并将这些发现与 181 例肝细胞癌（HCC）患者的临床结果相关联。还进行了内皮标志物 CD34 和血管抑素 1 与 Ki-67 的双重免疫染色，以评估 HCC 内皮细胞的血管生成活性。在血管抑素 1 阳性血管中，Ki-67 阳性内皮细胞的比例（22%）明显高于 CD34 阳性血管（9%，P<.001），提示血管抑素 1 与 HCC 内皮细胞的新生血管化之间存在相关性。MVD-CD34 减少，但根据组织学分级，由血管抑素 1 表达确定的 MVD 与 MVD-CD34 的比值（血管抑素 1/CD34）显著增加。血管抑素 1 与 FGF-2 的状态显著相关（P=.007），但与 VEGF-A 的状态无关（P=.055）。低血管抑素 1/CD34 组（血管抑素 1/CD34≤0.459）的 10 年总生存率和 2 年无病生存率显著高于高血管抑素 1/CD34 组（血管抑素 1/CD34>0.459）（生存率，48%比 38%和 52%比 35%；P<.001 和 P<.05）。此外，血管抑素 1/CD34 在 HCC 患者中是预后不良的独立标志物，这通过多变量分析确定（风险比，1.973；95%置信区间，1.049-3.711；P=.035）。血管抑素 1/CD34 可以识别增殖的血管，可能是预测 HCC 患者临床结果的有用生物标志物。
