【作者】 卢晓峰；

【导师】 孙淑明；

【作者基本信息】 汕头大学 ， 普通外科， 2007， 硕士

【摘要】 目的：粘附和降解是癌细胞浸润转移的两个关键步骤。MMP-7、TIMP-1与细胞外基质降解有关。E-CAD、Syndecan-1介导细胞-细胞(或基质)粘附。研究发现MMP-7可通过降解E-CAD破坏细胞连接。而Syndecan-1的表达与E-CAD有协同作用，且其能抑制MMPs的表达。我们采用免疫组化SP法检测MMP-7、TIMP-1、E-CAD、Syndecan-1在胃癌组织标本的表达情况，揭示它们与胃癌发生、发展的关系，评估胃癌中蛋白酶与细胞粘附的关系，以提高胃癌的早期诊治水平，也为临床应用蛋白酶抑制剂防治胃癌转移提供参考。方法：应用免疫组化SP法方法检测36例胃癌组织及36例癌旁组织中MMP-7、TIMP-1、E-CAD、Syndecan-1的表达水平，并分析胃癌中MMP-7、TIMP-1、E-CAD、Syndecan-1的表达与癌细胞浸润转移等有关临床病理因素的关系。结果：1．MMP-7在胃癌组织中的阳性表达率(58.33％)显著高于癌旁组织的阳性表达率(5.56％)(P＜0.01)。MMP-7的阳性表达与胃癌TNM分期(P＜0.01)及淋巴结转移(P＜0.05)均显著相关。2．TIMP-1在胃癌组织中的阳性表达率(44.44％)低于癌旁组织的阳性表达率(50.00％)，但无统计学意义(P＞0.05)。TIMP-1的阳性表达与胃癌TNM分期显著相关(P＜0.05)。3．E-CAD在胃癌组织中的阳性表达率(72.22％)显著低于癌旁组织的阳性表达率(91.67％)(P＜0.05)。E-CAD的阳性表达与胃癌分化程度显著相关(P＜0.05)。4．Syndecan-1在胃癌组织中的阳性表达率(55.56％)显著低于癌旁组织的阳性表达率(86.11％)(P＜0.01)。Syndecan-1的阳性表达与胃癌淋巴结转移及浸润深度显著相关(P＜0.05)。5．胃癌中E-CAD与Syndecan-1表达强度间存在正相关(P＜0.05)，MMP-7与TIMP-1、MMP-7与E-CAD、MMP-7与Syndecan-1的表达强度之间无统计学相关(P＞0.05)。结论：1．MMP-7在胃癌组织中的表达明显高于癌旁组织，E-CAD、Syndecan-1在胃癌组织中的表达明显低于癌旁组织，它们与胃癌的发生发展密切相关。2．MMP-7在胃癌中的高表达与胃癌TNM分期及淋巴结转移密切相关。TIMP-1的阳性表达与胃癌TNM分期显著负相关。E-CAD的阳性表达与胃癌分化程度显著正相关。Syndecan-1的阳性表达与胃癌淋巴结转移及浸润深度显著负相关。3．在胃癌组织中，E-CAD与Syndecan-1的表达密切相关，提示二者之间存在某种调控关系，二者协同参与了胃癌的浸润、转移过程。4．联合检测MMP-7、TIMP-1、E-CAD、Syndecan-1在胃癌中的表达，有助于进一步了解胃癌浸润转移的机制，预测胃癌的转移，判断其预后和选择治疗方案。更多还原

【Abstract】 Objective Adhesion and degradation are the two committed steps of cancer cells’ infiltration andmetastasis. Matrix metalloproteinase-7 (MMP-7) and tissue inhibitor of metalloproteinase-1(TIMP-1) are relevant to the degradation of extracellular matrix (ECM). Eptithelial cadherin(E-CAD) and Syndecan-1 (CD138) mediate the adhesion of cell-ceU or cell-matrix. It is foundthat MMP-7 can destroy the junction of cells by degradating E-CAD. And there is a synergisticeffect between the expressions of Syndecan-1 and E-CAD. Besides, Syndecan-1 can alsosuppress the expression of MMPs. We detect the expressions of MMP-7, TIMP-1, E-CAD andSyndecan-1 in 36 gastric carcinomas by immunohistochemistry for studying the relationshipbetween expressions of MMP-7, TIMP-1, E-CAD, Syndecan-1 and the invasion, metastasis ingastric carcinoma. It also can evaluate the relationship between MMPs and cell adhesion ingastric carcinoma and improve the diagnosis and treatment of gastric carcinoma. Even it canprovide information for clinical application of TIMPs in the prevention and cure of gastriccarcinoma.Methods Streptvidin-peroxidase immunohistochemistry technique (SP) was used to detect theexpressions of MMP-7, TIMP-1, E-CAD and Syndecan-1 in 36 gastric carcinoma specimens and36 gastric mucosa membrane beside carcinoma specimens. The relationship between theexpressions of MMP-7, TIMP-1, E-CAD and Syndecan-1 in gastric carcinoma and invasion,metastasis, clinicopathological features of gastric carcinoma was analyzed statistically.Results 1. The positive expression rate of MMP-7 in gastric carcinoma and mucosa membranebeside carcinoma were 58.33%, 5.56% respectively. The positive expression rate of MMP-7 ingastric carcinoma was higher than that in gastric mucosa membrane beside carcinoma (P＜0.01).The positive expression of MMP-7 was significantly correlated with TNM staging (P＜0.01) andlymph node metastasis (P＜0.05), but uncorrelated to age, sex, tumor size, intravascularinvolvement, lymphatic vessel invasion, infiltration depth, and differentiation (P＞0.05). 2. Thepositive expression rate of TIMP-1 in gastric carcinoma and mucosa membrane beside carcinomawere 44.44%, 50.00% respectively. The positive expression rate of TIMP-1 in gastric carcinomawas lower than that in gastric mucosa membrane beside carcinoma, but it was not significantstatistically (P＞0.05). The positive expression of TIMP-1 was significantly correlated with TNM staging (P＜0.01), but uncorrelated to age, sex, tumor size, intravascular involvement, lymphaticvessel invasion, infiltration depth, lymph node metastasis and differentiation (P＞0.05). 3. Thepositive expression rate of E-CAD in gastric carcinoma and mucosa membrane beside carcinomawere 72.22%, 91.67% respectively. The positive expression rate of E-CAD in gastric carcinomawas lower than that in gastric mucosa membrane beside carcinoma (P＜0.05). The positiveexpression of E-CAD was significantly correlated with differentiation (P＜0.05), but uncorrelatedto age, sex, tumor size, intravascular involvement, lymphatic vessel invasion, infiltration depth,lymph node metastasis and TNM staging (P＞0.05). 4. The positive expression rate of Syndecan-1in gastric carcinoma and mucosa membrane beside carcinoma were 55.56%, 86.11% respectively.The positive expression rate of Syndecan-1 in gastric carcinoma was lower than that in gastricmucosa membrane beside carcinoma (P＜0.01). The positive expression of Syndecan-1 wassignificantly correlated with lymph node metastasis and infiltration depth (P＜0.05), butuncorrelated to age, sex, tumor size, intravascular involvement, lymphatic vessel invasion,differentiation and TNM staging (P＞0.05). 5.18 in 36 cases of gastric carcinoma were positivelyexpressed both E-CAD and Syndecan-1 and 8 in 36 cases were negatively expressed bothE-CAD and Syndecan-1. It indicated strong relationship between the expression of E-CAD andSyndecan-1 (P＜0.05). But the relationships of MMP-7/TIMP-1, MMP-7/E-CAD andMMP-7/Syndecan-1 were not significant statistically (P＞0.05).Conclusion 1. The positive expression rate of MMP-7 in gastric carcinoma was higher thanthat in gastric mucosa membrane beside carcinoma. The positive expression rates of E-CAD andSyndecan-1 in gastric carcinoma were lower than that in gastric mucosa membrane besidecarcinoma. 2. The positive expression of MMP-7 was significantly correlated with TNM stagingand lymph node metastasis. The positive expression of TIMP-1 was significantly correlated withTNM staging. The positive expression of E-CAD was significantly correlated with differentiation.The positive expression of Syndecan-1 was significantly correlated with lymph node metastasisand infiltration depth. 3. The correlative expression between E-CAD and Syndecan-1 in gastriccarcinoma indicates that both of them play an important role in infiltration and metastasis ofgastric carcinoma cooperatively. 4. Combinative detection of MMP-7, TIMP-1, E-CAD andSyndecan-1 expressions in gastric carcinoma may be valued to recognize the mechanism oftumor invasion and metastasis, to evaluate the clinical progress of gastric carcinoma and to provide scientific basis for anti-angiogenesis in treatment of gastric carcinoma.更多还原