肺肉瘤样癌中血管生成拟态的形成及其与上皮间充质转化的关系

摘要

Objective: The expression and clinical significance of vasculogenic mimicry (VM) were investigated. The related mechanisms of epithelial-to-mesenchymal transition (EMT) in VM formation and worsening of pulmonary sarcomatoid carcinoma (PSC) were examined. Methods:Hematoxylin and eosin staining, CD31/periodic acid-Schiff double staining, and immunohistochemi-cal staining were performed to determine the expression of VM, Twist1, vascular endothelial growth factor (VEGF), E-cadherin, and vi-mentin in the tissues of 22 PSC patients. The clinical significance of VM and the mechanism of EMT in VM formation were explored. Results:VM was found in four (18.2%) of the 22 PSC patients. Kaplan–Meier survival analysis revealed that the patients with VM had a shorter survival period than those without the VM expression, with statistically significant differences found between the two groups. Comparative results of the groups with and without VM expression showed a higher positive rate of Twist1 expression in the former group (P<0.05). Significant correlations were observed between the Twist1 expression and the VEGF, E-cadherin, and vimentin expression. Conclusion:VM unfavorably influences the prognosis of PSC patients. Twist1 can upregulate Vimentin and downregulate E-cadherin by inducing EMT. Additionally, it may upregulate VEGF to promote VM formation, which increases tumor invasions and metastases.%　　目的：研究肺肉瘤样癌(pulmonary sarcomatoid carcinoma,PSC)中血管生成拟态(vasculogenic mimicry,VM)的临床意义,阐述上皮间充质转化(epithelial-to-mesenchymal transition,EMT)提高PSC的恶性度及促进VM形成的相关机制.方法：对肺肉瘤样癌组织切片22例进行HE、CD31和PAS双重染色,Twist、Vimentin、E-cadherin、VEGF免疫组织化学染色,分析VM相关的临床意义及EMT促进VM形成的相关机制.结果：22例中4例(18.2%)存在VM,Kaplan-Meier生存分析提示有无VM肿瘤患者比较生存时间差异有统计学意义(P<0.05).VM阳性患者Twist的阳性率较阴性患者高,且差异有统计学意义(P<0.05).Twist1的表达与VEGF、E-cadherin、Vimentin的表达存在明显相关性.结论：VM是患者预后的不利因素,肺肉瘤样癌中发生了EMT,转录因子Twist1可能通过下调E-cadherin,上调Vimentin诱导EMT,并可能通过上调VEGF的表达促进VM的形成,从而促进肿瘤的侵袭和转移.