【摘要】 目的:探讨胃腺癌(gastric adenocarcinoma,GAC)中是否存在血管生成拟态(vasculogenic mimicry,VM),并进一步阐述VM存在的临床病理意义,通过金属基质蛋白酶-2、9(matrix metalloproteinase,MMP-2、MMP-9)和组织蛋白酶D(Cathepsin D)的免疫组化染色,初步探讨VM的形成机制。方法:收集173例临床资料和随访资料完整的胃腺癌病例,通过过碘酸雪夫氏反应(Periodicacid-Schiff,PAS)与CD31双重染色和CK8&18免疫组化染色,将胃腺癌分成VM(+)组和VM(-)组,计数微血管密度(microvasculardensity,MVD)和血管拟态密度(vasculogenic mimicry density,VMD),并进行MMP-2、MMP-9和Cathepsin D的免疫组化染色。结果:173例胃腺癌患者中VM阳性者40例(23.12%),低分化腺癌组VM阳性率(26.4%)明显高于中分化腺癌组(4%)(χ~2=6.011,P=0.014);且VM(+)组更易发生血道转移和远期复发(χ~2=6.389,P=0.020;χ~2=4.748,P=0.029);血道转移组VMD计数较无转移组明显升高(t=3.140,P=0.003)。MVD在VM(+)组和VM(-)组中的差异无统计学意义(F=1.596,P=0.482)。Kaplan-Meier生存分析显示VM(+)组的生存率低于VM(-)组(P=0.022),Cox回归模型显示TNM分期和VM是影响胃腺癌患者生存率的危险因素。VM(+)组MMP-2、MMP-9和Cathepsin D的表达均高于VM(-)组(P均<0.05)。结论:胃腺癌中存在VM,且与分化程度有关,VM是胃腺癌不良预后的指标之一。MMP-2、MMP-9和CathepsinD可能参与了GAC中VM的形成。更多还原

【Abstract】 Objective:To explore whether vasculogenic mimicry (VM) exists in gastric adenocarcinoma (GAC) and to investigate the clinicopathologic significance of VM in GAC.Methods:We tended to illuminate the mechanism of VM by performing immunohistochemical staining of MMP-2,MMP-9 and Cathepsin D.A total of 173 GAC samples with detailed follow -up data were collected.CD31/ periodic acid-Schiff (PAS) double staining and CK8&18 immunohistochemical staining were performed to validate the existence of VM in GAC.The values of MVD (microvascular density) and VMD (vasculogenic mimicry density) were counted respectively.Immunohistochemical staining of MMP-2,MMP-9 and Cathepsin D was performed for all samples.Results:VM was observed in 40 of the 173 GAC samples,especially in poorly differentiated GAC (P=0.014).Patients with VM were prone to hematogenous metastasis and distant recurrence compared with those without VM (P=0.020,0.029).Higher VMD count was also associated with hematogenous metastasis (P=0.003).There was not significant difference in MVD count between VM-positive and VM-negative groups (F=1.596,P=0.482).The Kaplan-Meier survival analysis showed that the survival duration of the VM-positive group was significantly shorter than that of VM-negative group (P=0.022).Cox proportional hazards model indicated that the VM and TNM stage were independent predictors for poor prognosis of GAC (P=0.039 and 0.004).The immunohistochemical expression of MMP-2,MMP-9 and Cathepsin D was higher in VM-positive group than in VM-negative group (P<0.05).Conclusion:VM exists in GAC,especially in poorly differentiated GAC.VM is an unfavorable prognostic indicator for GAC.MMP-2,MMP-9 and Cathepsin D might involve the formation of VM in GAC.更多还原