Zhang Faming, Lin Hao, Cao Kaiyuan, Wang Hua, Pan Jincheng, Zhuang Jintao, Chen Xu, Huang Bin, Wang Daohu, Qiu Shaopeng
Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Research Center for Clinical Laboratory Standard, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, Guangdong, China.
Int J Urol. 2016 May;23(5):371-7. doi: 10.1111/iju.13070. Epub 2016 Feb 24.
To determine the prognostic role of vasculogenic mimicry in adrenocortical carcinoma, and to explore its relationship with vascular endothelial growth factor receptor 2 expression.
A total of 46 samples of adrenocortical carcinoma were collected and reviewed. Vasculogenic mimicry and vascular endothelial growth factor receptor 2 were detected by immunohistochemistry and double staining. Survival analysis was carried out to access pronostic significance. Three-dimensional culture method was applied to test the ability of vasculogenic mimicry formation by adrenocortical carcinoma cell lines SW-13 and H295R. Quantitative polymerase chain reaction and western blotting were used to monitor the expression of vascular endothelial growth factor receptor 2 in SW-13 and H295R. After being treated with specific inhibitor or small interfering ribonucleic acid to downregulate expression of vascular endothelial growth factor receptor 2, vasculogenic mimicry formation and cell prolifration of SW-13 cells were evaluated by 3-D culture and Cell Counting Kit-8 methods.
Vasculogenic mimicry was observed in 19 of the 46 (41.30%) adrenocortical carcinoma samples. Both vasculogenic mimicry and vascular endothelial growth factor receptor 2 expressions showed a positive association with Weiss score and TNM stage, whereas vascular endothelial growth factor receptor 2 was also associated with tumor size (all P < 0.05). Vasculogenic mimicry was closely correlated with vascular endothelial growth factor receptor 2 expressions (r = 0.470, P < 0.01). The median overall survival of patients with vasculogenicmimicry-positive or vascular endothelial growth factor receptor 2-positive was shorter than that of patients with vasculogenic mimicry-negative or vascular endothelial growth factor receptor 2-negative (P = 0.001 and 0.028, respectively). The vasculogenic mimicry-forming SW-13 cells expressed higher levels of vascular endothelial growth factor receptor 2 than that of H295R, which was unable to form vasculogenic mimicry on Matrigel. However, downregulation of vascular endothelial growth factor receptor 2 only decreased cell proliferation, but not vasculogenic mimicry formation by SW-13 cells.
Vasculogenic mimicry and overexpression of vascular endothelial growth factor receptor 2 seem to correlate with poor prognostic outcomes in adrenocortical carcinoma. Anti-angiogenesis treatments targeting vascular endothelial growth factor receptor 2 should be combined with therapies targeting vasculogenic mimicry in adrenocortical carcinoma.
确定血管生成拟态在肾上腺皮质癌中的预后作用，并探讨其与血管内皮生长因子受体2表达的关系。
收集并回顾46例肾上腺皮质癌样本。采用免疫组织化学和双重染色检测血管生成拟态和血管内皮生长因子受体2。进行生存分析以评估预后意义。应用三维培养方法检测肾上腺皮质癌细胞系SW-13和H295R形成血管生成拟态的能力。采用定量聚合酶链反应和蛋白质印迹法监测SW-13和H295R中血管内皮生长因子受体2的表达。在用特异性抑制剂或小干扰核糖核酸处理以下调血管内皮生长因子受体2的表达后，通过三维培养和细胞计数试剂盒-8方法评估SW-13细胞的血管生成拟态形成和细胞增殖。
46例肾上腺皮质癌样本中有19例（41.30%）观察到血管生成拟态。血管生成拟态和血管内皮生长因子受体2的表达均与Weiss评分和TNM分期呈正相关，而血管内皮生长因子受体2也与肿瘤大小相关（所有P<0.05）。血管生成拟态与血管内皮生长因子受体2的表达密切相关（r=0.470，P<0.01）。血管生成拟态阳性或血管内皮生长因子受体2阳性患者的中位总生存期短于血管生成拟态阴性或血管内皮生长因子受体2阴性患者（分别为P=0.001和0.028）。形成血管生成拟态的SW-13细胞比不能在基质胶上形成血管生成拟态的H295R表达更高水平的血管内皮生长因子受体2。然而，下调血管内皮生长因子受体2仅降低细胞增殖，但不影响SW-13细胞的血管生成拟态形成。
血管生成拟态和血管内皮生长因子受体2的过表达似乎与肾上腺皮质癌的不良预后相关。针对肾上腺皮质癌中血管内皮生长因子受体2的抗血管生成治疗应与针对血管生成拟态的治疗相结合。
