Smad4与β-catenin在儿童结肠息肉中的表达

发布时间：2018-10-18 07:44

【摘要】：目的研究Smad4与β-catenin在儿童肠息肉中的表达及作用机制。方法选取郑州大学第二附属医院病理科2005年7月-2013年4月手术儿童肠息肉蜡块标本60例，均为幼年性息肉。其中单发幼年性息肉36例（男性19例，女性17例，年龄3月-12岁，平均年龄6岁±2.1岁），多发幼年性息肉24例（男性14例，女性10例，年龄6月-9岁，平均4岁±1.3岁）；取成人结肠腺癌蜡块15例（男性8例，女性7例，年龄42-83岁，平均56±12.1岁），均为均为管状腺癌Ⅱ级；息肉旁正常肠黏膜组织标本10例（男性5例，女性5例，年龄5-13岁，平均7±1.2岁），均取自距息肉边缘大于7cm的正常肠黏膜组织。应用免疫组化的方法来测定所选标本中的β-catenin与Smad4蛋白的表达水平。结果 β-catenin蛋白表达情况：正常组中β-catenin蛋白主要为线性表达,蛋白染色为棕黄色颗粒，主要定位于细胞与细胞连接处的细胞膜，阳性率表达为100%；单发幼年性息肉组织中的β-catenin蛋白阳性表达率为80.56%（29/36），少数标本阴性表达（7例标本细胞浆表达，2例有胞浆和胞核有弱染色）；多发幼年性息肉组织中β-catenin染色阳性率为66.67%（16/24）（8例标本胞浆染色，3例标本胞浆与胞核染色）；大肠腺癌黏膜组织的β-catenin阳性率仅为26.7%（4/15），胞浆和胞核的表达明显增加，细胞膜表达有不同程度的减少。单发幼年性息肉组织与多发幼年性息肉组织中β-catenin蛋白均出现胞质和胞核染色。作为阳性对照的成人结肠低分化腺癌，β-catenin蛋白为异位表达。经过免疫组化定量分析，与正常对照组相比，β-catenin蛋白含量在单发幼年性息肉组、多发幼年性息肉组、腺癌组均有不同程度的增高，其差异有统计学意义。 Smad4蛋白表达情况:在正常对照组中Smad4蛋白阳性染色为胞浆或胞核中可见棕色或者黄色颗粒，其阳性率表达为100%；单发幼年性息肉组织中的Smad4蛋白染色为阳性，其阳性表达率为88.89%（32/36）；多发幼年性息肉组织中Smad4蛋白染色阳性较正常组及单发幼年性息肉组减弱，其阳性率为70.83%（17/24）；大肠腺癌组织的Smad4呈弱阳性或无表达，阳性率仅为46.67%（7/15）。单发幼年性息肉组与腺癌组染色阳性率经统计软件分析，差异有统计学意义；多发幼年性息肉组与腺癌组染色阳性率比较，差异无统计学意义。经过免疫组化定量分析，与正常对照组相比，Smad4蛋白表达均有不同程度降低。结论本研究所选取的儿童肠息肉标本中，不论单发幼年性息肉还是多发幼年性息肉，其β-catenin蛋白表达均较正常对照组有不同程度的增加，，且其在细胞的表达定位发生改变，由正常的膜线性表达转化为胞质和胞核中有不同程度的染色，提示癌基因β-catenin在儿童肠息肉的形成中起重要作用。而Smad4蛋白均有不同程度表达减低，且其染色情况有不同程度的减弱，表明抑癌基因Smad4在儿童肠息肉中的作用减弱。二者参与了儿童肠息肉发生、发展的过程。
[Abstract]:Objective to study the expression and mechanism of Smad4 and 尾-catenin in intestinal polyps in children. Methods from July 2005 to April 2013, 60 specimens of intestinal polyps were collected from Department of Pathology, second affiliated Hospital of Zhengzhou University, all of them were juvenile polyps. There were 36 cases of single juvenile polyps (male 19 cases, female 17 cases, 3-12 years old, mean age 6 卤2.1 years), and 24 cases of multiple juvenile polyps (male 14 cases, female 10 cases, 6-9 years old, mean 4 卤1.3 years old). 15 adult colon adenocarcinoma cases (male 8, female 7; age 42-83 years, mean 56 卤12. 1 years) were collected, and 10 specimens of normal intestinal mucosa adjacent to polyp were collected (male 5, female 5, age 5-13 years old). The average age was 7 卤1. 2 years old. All the normal intestinal mucosa tissues were obtained from the margin of the polyp larger than that of 7cm. The expression levels of 尾-catenin and Smad4 protein were determined by immunohistochemical method. Results the expression of 尾-catenin protein: in the normal group, 尾-catenin protein was mainly expressed linearly, and the protein was stained by brown granules, mainly located at the cell membrane at the junction between cell and cell, and the positive rate was 100%. The positive expression rate of 尾-catenin protein was 80.56% (29 / 36) in single juvenile polyps, and a few samples were negative (7 cases expressed in cytoplasm and 2 cases weakly stained in cytoplasm and nucleus). The positive rate of 尾-catenin staining was 66.67% (16 / 24) in multiple juvenile polyps (8 cases with cytoplasm staining, 3 cases with cytoplasm and nucleus staining), and the positive rate of 尾-catenin in colorectal adenocarcinoma mucosa was only 26.7% (4 / 15), the expression of cytoplasm and nucleus increased significantly. Cell membrane expression decreased in varying degrees. Cytoplasmic and nuclear staining of 尾-catenin protein was found in single juvenile polyps and multiple juvenile polyps. 尾-catenin protein was expressed ectopic in adult low differentiated adenocarcinoma of colon as a positive control. Compared with normal control group, 尾-catenin protein content was increased in single juvenile polyp group, multiple juvenile polyp group and adenocarcinoma group. The expression of Smad4 protein: in the normal control group, brown or yellow granules were found in the cytoplasm or nucleus, and the positive rate was 100%. The positive rate of Smad4 protein in single juvenile polyps was 88.89% (32 / 36), and the positive rate of Smad4 protein in multiple juvenile polyps was 70.83% (17 / 24). The positive rate of Smad4 was only 46.67% (7 / 15). The positive rate of staining in single juvenile polyp group and adenocarcinoma group was statistically significant, but there was no significant difference between multiple juvenile polyp group and adenocarcinoma group. Compared with the normal control group, the expression of Smad4 protein decreased in different degree by immunohistochemical quantitative analysis. Conclusion the expression of 尾-catenin protein in children with intestinal polyps was significantly higher than that in normal controls, regardless of single juvenile polyps or multiple juvenile polyps. The expression localization of 尾-catenin was changed from normal membrane linear expression to cytoplasmic and nuclear staining, suggesting that 尾-catenin plays an important role in the formation of intestinal polyps in children. However, the expression of Smad4 protein was decreased in different degree and its staining was weakened in different degree, which indicated that the role of tumor suppressor gene Smad4 in intestinal polyps in children was weakened. Both participate in the process of occurrence and development of intestinal polyps in children.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R735.35

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