【作者】 王胜昔；

【导师】 秦成勇；

【作者基本信息】 山东大学 ， 内科学， 2009， 硕士

【摘要】 背景及目的:胃癌是世界范围内最常见的恶性肿瘤之一,严重危害人们生命健康,其发病机制尚不清楚,胃癌的侵袭转移是导致患者死亡的重要原因。目前认为上皮细胞—间质细胞转化(epithelial-mesenchymal transition,EMT)对肿瘤的侵袭和转移有重要影响,其中Snail及钙黏蛋白E-cadherin、N-cadherin在EMT的发生机制中起了重要作用,因此推断Snail、E-cadherin及N-cadherin在胃癌的发生、发展及转移中起了重要作用。本研究观察Snail、E-cadherin及N-cadherin蛋白在胃腺癌组织中的表达及意义,探讨它们在胃癌发生、发展中的作用及其临床应用价值。方法:收集112例手术切除的胃溃疡型腺癌组织标本,同时取79例癌旁组织作为对照。应用免疫组织化学S-P法检测胃腺癌组织、癌旁组织中Snail、E-cadherin及N-cadherin蛋白的表达,并与临床病理资料作对照,统计软件采用SPSS17.0,统计方法采用χ~2检验、表达相关性采用Spearman等级相关分析。结果:(1)Snail在胃腺癌组织阳性表达率为82.1%,高于癌旁组织的阳性表达率35.4%,差异具有显著性(P＜0.05);Snail在低分化组阳性表达率显著高于高、中分化组(P＜0.05);侵及浆膜组Snail的阳性表达率为86.5%,显著高于未侵及浆膜组的阳性表达率65.2%(P＜0.05);有淋巴结转移组Snail阳性表达率为90.0%,显著高于无淋巴结转移组的阳性表达率69.1%(P＜0.05);有远处转移组Snail阳性表达率为100%,显著高于无远处转组的阳性表达率79.8%(P＜0.05);Snail的表达与性别、年龄、肿瘤大小、肿瘤部位及临床分期无关(P＞0.05)。(2)E-cadherin在胃腺癌组织阳性表达率为33.9%,显著低于癌旁组织中阳性表达率100%(P＜0.05);低分化组E-cadherin阳性表达率显著低于高、中分化组(P＜0.05);E-cadherin在侵及浆膜组的阳性表达率为29.2%,显著低于未及浆膜组的阳性表达率52.2%(P＜0.05);E-cadherin在有淋巴结转移组阳性表达率为24.3%,低于无淋巴结转移组的阳性表达率50%(P＜0.05);在临床分期中,E-cadherin在Ⅲ、Ⅳ期组阳性表达率为25.6%,显著低于Ⅰ、Ⅱ期阳性表达率52.9%(P＜0.05):E-cadherin在有远处转移组阳性表达率为7.1%,显著低于无远处转移组阳性表达率37.4%(P＜0.05)。E-cadherin的表达与性别、年龄、肿瘤大小及肿瘤部位均无关(P＞0.05)。(3)N-cadherin在胃腺癌组织阳性表达率83.3%,显著高于癌旁组织中阳性表达率41.25%(P＜0.05);N-cadherin在低分化组阳性表达率显著高于高、中分化组(P＜0.05):N-cadherin在侵及浆膜组的阳性表达率为53.9%,显著高于未及浆膜组阳性表达率26.1%(P＜0.05);N-cadherin在有淋巴结转移组阳性表达率为60.0%,显著高于无淋巴结转移组的阳性表达率28.6%(P＜0.05),N-cadherin的表达与性别、年龄、肿瘤大小、肿瘤部位及临床分期无关(P＞0.05)。(4)胃腺癌组织中Snail和E-cadherin的表达呈明显负相关(r=-0.212,P＜0.05):E-cadherin和N-cadherin的表达呈明显负相关(r=-0.243,P＜0.05)。结论:E-cadherin低表达与Snail高表达及N-cadherin的反常表达在胃腺癌的发生、发展过程中可能发挥重要作用,并与胃腺癌的浸润及转移有密切关系;联合检测Snail、E-cadherin与N-cadherin蛋白对预测胃癌浸润转移有重要意义。更多还原

【Abstract】 Objective: Gastric carcinoma (GC) is one of the most common malignant tumors in the world that severely threatens people’s health, and its mechanism is still unknown,the invasion and metastasis of GC is an important cause of death. Researches show that the EMT is responsible for the invasion and metastasis of tumor,and the Snail protein and the adhesion proteins E-cadherin、N-cadherin in the occurrence of the EMT have played an important role ,so we can infer that Snail、E-cadherin and N-cadherin played an important role in the invasion and metastasis of GC.We investigate the expression of Snail、E- cadherin and N-cadherin protein in gastric adenocarcinoma and their significance to explore their roles in carcinogenesis, invasion and metastasis of gastric adenocarcinoma and to evaluate their clinicopathologic significances.Method: The expression of Snail、E-cadherin and N-cadherin proteins in 112 cases of gastric adenocarcinoma and 79 cases of adjacent tissues were detected by immunohistochemical S-P method, and the correlation with clinicopathological features was analyzed. We useχ~2 test and Spearman rank correlation analysis method to analysis with the help of SPSS 17.0.Results: (1) The positive rate of Snail immunostaining in gastric adenocarcinoma (82.1%)was higher than that in adjacent tissues(35.4%)(P<0.05);The expression of Snail was significantly related with the differential degree、depth of tumour invasion, lymph node metastasis and distant metastasis (P<0.05), but they did not correlate with sex, age, tumour size and clinical stage(P>0.05).(2) The positive rate of E-cadherin immunostaining in gastric carcinoma(33.9%) was lower than that in adjacent tissues(100%)(P<0.05); The expression of E-cadherin was significantly related with the differential degree、histologic type, depth of tumour invasion、lymph node metastasis、distant metastasis and clinical stage(P<0.05), but they did not correlate with sex, age, tumour size(P>0.05).(3) The positive rate of N-cadherin immunostaining in gastric adenocarcinoma (83.3%)was higher than that in adjacent tissues(41.25%)(P<0.05);The expression of N-cadherin was significantly related with the differential degree、depth of tumour invasion, lymph node metastasis and distant metastasis (P<0.05), but they did not correlate with sex, age, tumour size and clinical stage(P>0.05).(4) A negative correlation was found between the expression of Snail protein and E-cadherin protein(r=-0.212, P<0.05). A negative correlation was found between the expression of N-cadherin protein and E-cadherin protein(r=-0.243, P<0.05).Conclusions: The increased expression of Snail、the decreased expression of E-cadherin and the abnormal expression of N-cadherin may play an important role in the development of gastric adenocarcinoma, and they are involved in the processes of invasion and metastasis of gastric adenocarcinoma. The combined detection of E-cadherin、N-cadherin and Snail has positive effects on predicting the invasion and metastasis in gastric adenocarcinoma.更多还原