【作者】 夏雪雁；

【导师】 李连宏；

【作者基本信息】 大连医科大学 ， 病理学与病理生理学， 2005， 硕士

【摘要】 背景与目的: 胃癌是最常见的恶性肿瘤之一,大量研究证明,胃癌的发生常常经历一个相当长的演变阶段,即癌前病变。目前,有关胃癌及胃癌前病变的发生机制还不完全清楚。分子生物学的发展和应用使人们认识到由正常胃黏膜—癌前病变—胃癌的演变是多基因变化、多阶段过程。因此,寻求不同阶段的肿瘤相关基因与胃癌前病变发生的关系,有助于揭示胃癌前病变的发生机制和胃癌发生的关系及胃癌的早期诊断和预防。 Survivin 基因是近几年被发现的一种新的凋亡抑制基因,是凋亡抑制因子 IAP(inhibitor of apoptosis protein)家族的成员。Survivin 只在胚胎和肿瘤组织中表达,在正常成人分化组织中(胸腺、生殖器除外)检测不到。在多步骤肿瘤发生的早期,各种因素导致的凋亡抑制不仅有利于细胞的继续增殖,还有利于异常基因的进一步积聚,促使细胞恶性转化,从而有助于肿瘤的发生发展。 抑癌基因在控制细胞生长,增殖及分化过程中起者十分重要的负调节作用,并能潜在的抑制肿瘤生长,其功能失活可导致细胞恶性转化,肿瘤发生。PTEN(Phosphatase and tensin homologu deleted on chromosometen)是第一个被发现的具有磷酸酶活性的抑癌基因。PTEN有抑制生长,促进细胞凋亡的作用,并能抑制细胞黏附及肿瘤转移。P53 基因是迄今为止所发现的与人类肿瘤相关性最高的基因,是重要的2抑癌基因,分为野生型和突变型。P53 基因表达 P53 蛋白的生化功能为调节因子,对细胞周期中的增殖细胞具有调控作用。Ki-67 是一种敏感的细胞增殖相关核抗原,可反映肿瘤细胞的增殖活性。在多种肿瘤及癌前病变中均有ki-67的异常表达,与肿瘤的种植、浸润、转移潜能密切相关。本实验通过检测胃癌及癌前病变组织中的凋亡抑制基因 Survivin和抑癌基因 PTEN、P53 以及增殖核抗原 ki-67 的表达及相关性,分析其在胃癌前病变和胃癌发生发展中的作用及其相关性。探讨肿瘤相关基因的蛋白表达在胃癌早期诊断和预防的可能性。方法:应用免疫组织 SP 法检测 Survivin、PTEN 和 P53 及 ki-67蛋白在 10 例正常胃黏膜组织、33 例浅表性胃炎、30 例萎缩性胃炎(无肠化)、33 例萎缩性胃炎(伴肠化)、31 例异型增生胃黏膜、25 例胃癌中的表达。采用 SPSS12.0 统计软件对数据进行录入与管理,采用 χ2检验对结果进行统计分析。结果: Survivin、PTEN、突变型 P53 及 ki-67 蛋白在正常胃黏膜组织的表达率分别为 0%、100%、0%、0%;在浅表性胃炎的表达率分别为 0%、100%、0%、18%;在萎缩性胃炎(无肠化)黏膜中表达率分别为 0%、93%、0%、33%;在萎缩性胃炎(伴肠化)黏膜中表达率分别为 0%、91%、0%、39%;在轻度异型增生胃黏膜中的表达率分别为 7%、77%、7%、54%;在中度异型增生胃黏膜中的表达率分别为 20%、70%、30%、60%;在重度异型增生胃黏膜中的表达率分别为 50%、63%、63%、75%;在胃癌组织中表达率分别为 56%、60%、68%、88%。Survivin 在异型增生胃黏膜和胃癌组织中有阳性表达,且重度异型增生与胃癌组织间无显著差异(p>0.05)。PTEN 在各胃黏膜组织中均有阳性表达,其中异型增生和慢性萎缩性胃炎有显著差异(p<0.05),异型增生与胃癌组织之间无显著差异(p>0.05)。突变型 P53 基因在正常胃黏膜,浅表性胃炎和萎缩性胃炎中不表达,在重度异型增生与胃癌组织间无显著差异(p>0.05)。Ki-67 在正常胃黏膜中不表达,在异型增生与胃癌组织间有显著差异(P<0.05)。在异型增生和胃癌组织中 Survivin 与突变型 P53 基因的表更多还原

【Abstract】 Background & Objective: Gastric carcinoma remains one of the most common carcinomas,lots of research have been shown that the develping of gastric carcinoma undergo a long stage- gastric precancerous lesion. People have not know clearly the mechanism of gastric carcinoma by now. With the develping of molecular biology , people have know that from normal gastric mucosa to gastric carcinoma often involve many genes and many biology processes. It will help to explain the mechanism of gastric carcinoma and the early diagnosing gastric carcinoma,if the relationship between the different tumor genes and the gastric precancerous lesion could be found. Survivin gene is a novel inhibitor gene of apoptosis and is a new member of inhibitor of apoptosis protein .Survivin only expresses in the tissue of embryo and tomor.It can not be detected in the normal tissue. In the physiological condition,Survivin can clear away the old and abnomal cell by the apoptosis of cell . In the early stage,many factors which lead to inhibite cell apoptosis were benefit of proliferation of cells and abnomal genes accumulation and the develping of gastric carcinoma. Tumor suppressor genes,which inhabit cells growth and proliferation, have a potential function in preventing the occurrence and growth of tumors. Phosphatase and tensin homologue deleted on chromosometen (PTEN) , the first identified suppressor gene that have phosphatase activity,has an important role in signals condition . p53 gene have highly correlated with human tumors . p53 protein has a function in regulating the proliferation cells of cellcycle. Ki-67 is a nuclear which connected with proliferation cells. Many tumors and precancerous lesions can be detected the expression of ki-67.It might play an important role in regulating process of tumor invasion and metastasis. The present study was designed to investigate the protein expression of Survivin, PTEN, p53, ki-67 and their relationships in the gastric precancerous lesion and gastric carcinoma,and to assess the possibility for the early diagnosing gastric carcinoma with tumor gene Methods: The immunohistochemical SP method was applied to examine the expression of Survivin, PTEN, p53 and ki-67 in normal gastric mucosa ,chronic superficial gastritis, atrophic gastritis without intestinal metaplasia,atrophic gastritis with intestinal metaplasia, mild dysplasia moderate dysplasia, severe dysplasia and gastric carcinoma. The data were processed with SPSS 12.0. Results: The positive expression rates of Surviving , PTEN ,p53 and ki-67 were 0%、100%、0%、0%,respectively ,in normal gastric mucosa. The positive expression rates of theirs were 0%、100%、0%、18%,respectively, in chronic superficial gastritis.The positive rates of theirs were 0%、93%、0%、33%, respectively, in atrophic gastritis without intestinal metaplasia. The positive expression rates of theirs were 0%、91%、0%、39% respectively, in atrophic gastritis with intestinal metaplasia. The positive rates of theirs were 7%、77%、7%、54% , respectively, in mild dysplasia. The positive rates of theirs were 20%、70%、30%、60% ,respectively, in moderate dysplasia. The positive rates of theirs were 50%、63%、63%、75%,respectively, in severe dysplasia. The positive rates of theirs were 56%、60%、68%、88% ,respectively,in gastric carcinoma The positive expression rate of Survivin was observed in dysplasia and carcinoma.No significant difference was observed for Survivin expression level between severe dysplasia and carcinoma(p>0.05). The positive expression rate of PTEN was observed and was down regulated in the in gastric carcinoma and precancerous lesion . No significant difference was observed for PTEN expression level between dysplasia and carcinoma(p>0.05).No significant difference was observed for p53 expression level between severe dysplasia and carcinoma(p>0.05). The positive rate of ki-67 was observed and was up regulated in the in gastric carcinoma and precancerous lesion . No significant difference was observed for PTEN expression level between dysplasia and c更多还原