Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors
Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors
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DOI：
10.1016/j.humpath.2007.07.018
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发表时间：
2008-03-01
期刊：
影响因子：
3.3
通讯作者：
Zhang, Lihua
中科院分区：
文献类型：
--
作者：
Sun, Baocun;Qie, Shuo;Zhang, Lihua
血管生成拟态（VM）是由高度侵袭性和遗传失调的肿瘤细胞形成的流体传导通道。在这项研究中，我们收集了84例胃肠道间质瘤（GIST）的标本，沿着临床病理资料，并收集了另外42例GIST的新鲜组织，用于明胶酶谱。CD 31/HIO-Schiff双染及CD 117和CD 31免疫组化染色显示，21例GIST中有VM。核分裂率>= 5/50高倍视野的病灶与核分裂率较低的病灶之间VM阳性率有显著差异（P = .000），有肝转移的病例与无肝转移的病例之间VM阳性率有显著差异（P = .008）。高风险组（5.9%）与极低/低风险组（12.5%）（P = 0.010）或中等风险组（39.5%）（P= 0.020）之间VM阳性率存在显著差异。Kaplan-Meier生存分析显示VM预后差（P = .0000）。考克斯比例风险模型显示VM的存在、肿瘤大小≥ 10 cm和出血是预后不良的独立预测因子（分别为P = 0.000，0.005，0.032）。基质金属蛋白酶（MMP）-2和MMP-9的染色指数在VM阳性组高于VM阴性组（P = 0.024和0.037，分别）。明胶酶谱显示，MMP-2和MMP-9的活性在VM阳性病变中显著较高（分别为P = 0.013和0.033）。我们的结论是，胃肠道间质瘤的VM是一个不利的预后迹象，VM阳性肿瘤患者容易遭受肝转移。MMP-2和MMP-9在GIST VM形成中起重要作用。(c)2008年爱思唯尔公司All rights reserved.
Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically dysregulated tumor cells. In this study, we collected specimens of 84 human gastrointestinal stromal tumors (GISTs) along with clinicopathologic data and another 42 GISTs with fresh tissue that was used for gelatin zymography. VM was found in 21 of the 84 GISTs using CD31/ periodic acid-Schiff double staining and CD117 and CD31 immunohistochemical staining. There was a significant difference in the VM-positive rate between the lesions with a mitotic rate >= 5/50 high-power fields and those with a lower mitotic rate (P = .000) and between the cases with and without liver metastasis (P = .008). There was a significant difference in the VM-positive rate between the high-risk group (5.9%) and the very low/low-risk group (12.5%) (P = .010) or the intermediate-risk group (39.5%) (P=.020). Kaplan-Meier survival analysis showed VM indicated a poor prognosis (P = .0000). Cox proportional hazards model indicated that the presence of VM, tumor size 10 cm or greater, and hemorrhage were independent predictors of a poor prognosis (P = .000,.005,.032, respectively). The staining indexes of matrix metalloproteinase (MMP)-2 and MMP-9 were higher in the VM-positive than in the VM-negative group (P = .024 and .037, respectively). Gelatin zymography showed that the activity of MMP-2 and MMP-9 was significantly higher in the VM-positive lesions (P = .013 and .033, respectively). We conclude that VM in GISTs is an unfavorable prognostic sign and that patients with VM-positive tumors are prone to suffer liver metastasis. Both MMP-2 and MMP-9 play an important role in VM formation in GISTs. (c) 2008 Elsevier Inc. All rights reserved.