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（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.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第7期372-376,共5页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金资助(编号:30770828,30830049)
