Ren Ke, Yao Nan, Wang Guangye, Tian Lei, Ma Jie, Shi Xin, Zhang Lei, Zhang Jian, Zhou Xing, Zhou Guangxin, Wu Sujia, Sun Xiaoliang
Department of Orthopedics, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Changzhou City 213003, Jiangsu Province, People's Republic of China.
Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing City 210028, Jiangsu Province, People's Republic of China.
Hum Pathol. 2014 Oct;45(10):2120-9. doi: 10.1016/j.humpath.2014.06.013. Epub 2014 Jun 30.
Vasculogenic mimicry (VM), a formation of nonendothelial microvascular channels, has been generally recognized as a new pattern of neovascularization in aggressive malignancies. However, whether VM is present and clinically significant in osteosarcoma remains unknown. We identified VM by CD34/periodic acid-Schiff double staining of osteosarcoma specimens before chemotherapy and investigated its prognostic implications. Tumors were also immunohistochemically stained for focal adhesion kinase (FAK) and migration inducing gene 7 (Mig-7) to determine whether these markers are associated with the occurrence of VM. VM was found in 15 of 66 osteoblastic-type osteosarcoma samples (22.7%), and the incidence of VM did not differ with respect to patient sex, age, tumor size, tumor site, surgical type, or histologic response to preoperative chemotherapy. However, Kaplan-Meier survival analysis determined that the presence of VM and the tumor necrosis rate after preoperative chemotherapy are associated with both the overall survival (P = .011 and P = .040, respectively) and metastasis-free survival (P = .002 and P = .045, respectively). Furthermore, Cox proportional hazards analysis showed that the presence of VM and the histologic response to preoperative chemotherapy were independent indicators for both poor overall survival (P = .007 and P = .024, respectively) and poor metastasis-free survival (P = .002 and P = .027, respectively). The expression level of FAK and Mig-7 were higher in the VM group than the non-VM group (P = .017 and P = .021, respectively). These results demonstrate the presence of VM in osteoblastic osteosarcoma and suggest that VM is an unfavorable prognostic factor with FAK and Mig-7 expressions as a potential mechanism of VM formation in osteosarcoma.
血管生成拟态（VM）是一种非内皮微血管通道的形成，已被普遍认为是侵袭性恶性肿瘤中新的血管生成模式。然而，骨肉瘤中是否存在VM及其临床意义仍不清楚。我们通过对化疗前骨肉瘤标本进行CD34/过碘酸希夫双重染色来识别VM，并研究其预后意义。还对肿瘤进行了局灶黏附激酶（FAK）和迁移诱导基因7（Mig-7）的免疫组织化学染色，以确定这些标志物是否与VM的发生有关。在66例成骨细胞型骨肉瘤样本中，有15例发现了VM（22.7%），VM的发生率在患者性别、年龄、肿瘤大小、肿瘤部位、手术类型或术前化疗的组织学反应方面没有差异。然而，Kaplan-Meier生存分析确定，VM的存在和术前化疗后的肿瘤坏死率与总生存率（分别为P = 0.011和P = 0.040）和无转移生存率（分别为P = 0.002和P = 0.045）均相关。此外，Cox比例风险分析表明，VM的存在和术前化疗的组织学反应是总生存率差（分别为P = 0.007和P = 0.024）和无转移生存率差（分别为P = 0.002和P = 0.027）的独立指标。VM组中FAK和Mig-7的表达水平高于非VM组（分别为P = 0.017和P = 0.021）。这些结果证明了成骨细胞性骨肉瘤中存在VM，并表明VM是一个不良预后因素，FAK和Mig-7的表达是骨肉瘤中VM形成的潜在机制。
