Relationship between vasculogenic mimicry and epithelial-to-mesenchymal transition in pulmonary sarcomatoid carcinoma
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摘要:
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。 Abstract: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 immunohistochemical staining were performed to determine the expression of VM, Twist1, vascular endothelial growth factor(VEGF), E-cadherin, and vimentin 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. -
图 1 肺肉瘤样癌中VM的CD31和PAS双重染色及生存分析
Figure 1. VM expression determined by CD31/periodic acid Schiff dou-ble staining and Kaplan–Meier survival analysis in PSC
A and B: Endothelial-dependent vessel was CD31(+)and PAS(+)(redarrows)(CD31/PAS double-staining, ×400).The VM channel formedby the tumor cells was CD31(-), and the base membrane-like structurebetween the red blood cells and tumor cells was PAS(-)(black arrow)(CD31/PAS double-staining, ×400).C: Kaplan–Meier survival analy-sis indicated that the VM(+)PSC patients have shorter survival timethan the VM(-)PSC patients
图 2 Twist1在VM(+)组和VM(-)组的表达
Figure 2. Twist1 in the VM(+)and VM(-)groups(IHC staining, ×400)
图 3 VEGF、E-cadherin和Vimentin在Twist1(+)和Twist1(-)组的差异性表达
Figure 3. Differential expression of VEGF, E-cadherin, and Vimentin in the Twist1(+)and Twist1(-)PSC groups
表 1 VM、Twist1与临床病理资料的关系
Table 1. Correlation of VM and Twist1 with clinicopathologic characteristics of PSC
表 2 VM(+)组和VM（-）组之间Twist1的差异表达
Table 2. Relationship between VM and Twist1 expression
表 3 Twist1的表达与E-cadherin、Vimentin、VEGF表达的相关性
Table 3. Twist1 expression in correlation with VEGF, E-cadherin and Vimentin
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