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(CathepsinD)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(Penodic acid—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(microvascular density,MVD)和血管拟态密度(vasculogenic mimicry density,VMD),并进行MMP-2、MMP-9和CathepsinD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%)(X^2=6.011,P=0.014);且VM(+)组更易发生血道转移和远期复发(X^2=6.389,P=-0.020;X^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Cathepsin D可能参与了GAC中VM的形成。
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.