【作者】 程道博；

【导师】 赵立群；

【作者基本信息】 郑州大学 ， 内科学， 2010， 硕士

【摘要】 食管癌近年来发病率虽然有所降低,但是因为缺乏有效的早期发现、诊断方法,发现时大都已处于中晚期,治疗效果不佳。寻找一种或者多种特异性较高的肿瘤生物学标志物是大家共同的期待。抗凋亡蛋白survivin在细胞凋亡和细胞分裂中发挥着双重作用,近年来的研究发现,该蛋白与食管鳞癌组织的分化和肿瘤细胞的浸润有较大关系,可能是与survivin的高表达抑制了细胞凋亡、促进肿瘤细胞的蔓延有关。本研究通过免疫组织化学方法探讨survivin在食管癌组织和癌周组织中的表达与分化状态、浸润深度等临床病理特征的关系,检测了体外培养的食管鳞癌细胞中survivin表达并分析了其与细胞分化的相关性,提示survivin蛋白可能为食管癌分化和浸润过程中较为特异的标志物。Ki-67是一种较明确的细胞增值抗原。1.采用免疫组化SP法分别对40例食管鳞癌组织中及20例癌旁组织中Survivin、Ki-67的表达情况进行检测。2.用免疫细胞化学方法分别检测人食管上皮永生细胞系及不同分化程度的鳞状上皮肿瘤细胞系中Survivin的表达情况。3.采用SPSS13.0统计软件,根据资料类型,统计方法采用X2检验及Continuity Correction连续矫正检验和直线相关回归分析。P<0.05为有统计学差异。1.Survivin、Ki-67在食管鳞癌组织和癌旁组织中表达情况肿瘤组织中survivin、ki-67两种蛋白的阳性表达和癌周正常组织明显不同,有统计学意义(P<0.05)。2. Survivin、Ki-67在食管鳞癌组织中的表达与临床病理关系Survivin蛋白在浸润之浅层、深层肿瘤组织阳性率明显不同,组间阳性率差异明显,在统计学上有意义(P<0.05)；不同分化状态肿瘤组织阳性率组间差异有统计学意义(P<0.05),其表达高低与临床其它病理特征没有明显的关系。Ki67蛋白在浸润之浅层、深层肿瘤组织阳性表达明显不同,组间阳性率差异有统计学意义(P<0.05)；不同分化状态肿瘤组织中阳性率组间差异明显,统计学上有意义(P<0.05),其表达高低与临床其它病理特征无相关性。3.食管鳞癌组织中Survivin和Ki-67蛋白表达的相互关系Spearman等级相关方法检验分析显示,Survivin和Ki-67蛋白在食管鳞癌组织中的表达呈正相关(P<0.05)。4. KRSE-70细胞系survivin蛋白阳性表达率为85%,KYSE-450细胞系表达率为53.8%,Het-1A细胞系表达率为5.3%。3系不同分化状态的细胞survivin阳性表达率有明显的不同,统计学上有意义(P<0.01)。1. Survivin在食管鳞癌组织及体外培养的鳞癌细胞中的表达明显高于正常组织,且与患者年龄、性别、淋巴结转移等无关,与肿瘤组织浸润深度、分化程度有明显关系。2.Ki-67在食管鳞癌组织中的表达明显高于正常组织,且与患者年龄、性别、淋巴结转移无关,与肿瘤组织浸润深度、分化程度有明显关系。3. survivin与ki-67在食管鳞癌组织中的表达一致,具有明显的相关性。4.联合检测食管鳞癌中survivin和ki67蛋白的表达,可以提示食管癌的发生及分化程度,为治疗方法的选择提供一定理论依据。更多还原

【Abstract】 Esophageal cancer is a common gastrointestinal tumor. Its low early diagnosis rate has led to a large proportion of esophageal cancer detected in mid and late stage, resulting in poor treatment outcome. Thus, the key to its treatment is early detection, which requires highly specific biological marker.Anti-apoptotic protein survivin plays a dual role in apoptosis and cell division. Recent studies have found close relation between survivin and differentiation of esophageal squamous cell carcinoma as well as infiltration of tumor cells. A high survivin expression is also proposed in suppressed apoptosis and in metastasis. Using immunohistochemical methods, the present study demonstrated the relation of cellular differentiation status and invasion depth to survivin expression in esophageal squamous cell carcinoma. It was also hoped that the results of this study would strengthen current body of evidence for specific biological marker in detection of early esophageal cancer and esophageal cancer differentiation. Ki-67 is a more specific cell proliferation antigen.1. The levels of expression of surviving and Ki-67 were detected using immunohistochemical SP from 40 samples of esophageal squamous cell carcinoma and 20 samples of adjacent tissues.2. Using immune chemical methods, the levels of expression of surviving in normal esophageal epithelial cells (Het-IA), well-differentiated esophageal squamous epithelial cells (KYSE-70) and poorly differentiated squamous cell epithelial cells (KYSE-450).3. Statistical analysis, continuity correction and X2 test, were performed using SPSS 13.0. (P≤0.05 was designated to be statistically significant).1. Expression of survivin, ki-67 in esophageal squamous cell carcinoma and adjacent tissuesEsophageal cancer survivin, ki-67 gene expression was significantly different from the adjacent tissue (P<0.05).2. Survivin, Ki-67 in esophageal squamous cell carcinoma and the clinical pathology Statistically significantly difference in Survivin and Ki-67 expressions were found in tumours of different invasion depth and different differential status (p<0.05).Levels of Survivin and Ki-67 expressions were not found to be influenced by other pathological characteristics.3. Expression of Survivin and Ki-67 in esophageal squamous cell carcinoma Spearman rank correlation method of test analysis showed a positive correlation between the expression of Survivin and Ki-67 protein in esophageal squamous cell carcinoma (P<0.05).4. Survivin expression in KRSE-70 cells, KYSE-450 cells and Het-IA cells were 85%,53.8% and 5.3% respectively. Statistically significant difference in the levels of Survivin expression were found in abovementioned cell lines of different differentiatial status (P<0.01).The expression of Survivin and Ki-67 in squamous cell carcinoma was significantly higher than that in normal tissue. The levels of expression were found to have positive correlation with the status of differentiation and invasion, while age, gender and lymph node appeared to have minimal relation to the expression.更多还原