血管生成拟态在胃腺癌中的临床病理意义和相关机制研究*

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（Periodic 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%）（χ2=6.011，P=0.014）；且VM（+）组更易发生血道转移和远期复发（χ2=6.389，P=0.020；χ2=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。 

Mechanism of Vasculogenic Mimicry and Its Clinicopathologic Significance in Gastric Adenocarcinoma

Objective:To explore whether vasculogenic mimicry(VM)exists in gastric adenocarcinoma(GAC)and to in-vestigate the clinicopathologic significance of VM in GAC.Methods:We tended to illuminate the mechanism of VM by per-forming immunohistochemical staining of MMP-2,MMP-9 and Cathepsin D.A total of 173 GAC samples with detailed fol-were performed to validate the existence of VM in GAC.The values of MVD(microvascular density)and VMD(vasculogen-ic mimicry density)were counted respectively.Immunohistochemical staining of MMP-2,MMP-9 and Cathepsin D was per-formed 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 sig-nificant difference in MVD count between VM-positive and VM-negative groups(F=1.596,P=0.482).The Kaplan-Meier sur-vival 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.