【作者】 张晶；

【导师】 孙秀华；

【作者基本信息】 大连医科大学 ， 肿瘤学， 2011， 硕士

【摘要】 背景:胃癌在我国是常见的恶性肿瘤之一,多数患者确诊时已是晚期,预后差,生存期短,严重影响我国人民身体健康,故与胃癌预后相关的因素一直以来就备受临床关注。胃癌的发生、发展涉及到多基因、多蛋白水平的变化。Her-2/Neu是原癌基因c-erbB-2(Her-2/Neu)编码的具有受体酪氨酸酶(receptor-tyrosine kinase, RTKs)活性的跨膜糖蛋白,能启动酪氨酸激酶调控的信号转导系统。Ki-67是一种核蛋白,具有非组蛋白的特点,与细胞有丝分裂有关,是目前应用最广泛的评估肿瘤细胞增殖的方法之一。本研究旨在探讨Her-2/Neu和Ki-67在不同类型胃癌中的表达情况、与临床病理特征的关系及与预后的相关性,为临床治疗及评估预后提供参考。目的:检测Her-2/Neu和Ki-67在不同胃癌组织中的表达,分析Her-2/Neu和Ki-67的表达与临床病理特征的相关性及其对预后的影响,Her-2/Neu和Ki-67表达之间的相关性及对预后的影响。方法:应用免疫组化二步法,检测60例胃癌患者术后标本中Her-2/Neu和Ki-67的表达情况,并结合临床病理特征及随访资料进行综合分析。采用四格表Chi-square检验和Fisher确切概率法分析Her-2/Neu和Ki-67在不同组织类型胃癌中的表达是否有差异;采用Spearman进行等级相关分析,分析Her-2/Neu和Ki-67分别表达及双表达与临床病理特征的相关性,采用Kaplan-Meier法和Log-rank检验进行生存期分析,分析Her-2/Neu和Ki-67分别表达及双表达对胃癌术后患者无病生存期及总生存期的影响。结果:1.在60例胃癌组织中Her-2/Neu和Ki-67表达为阳性者分别为29例(48.3%)和31例(65%),二者在不同组织类型的胃癌中表达无差异。2.Her-2/Neu的表达与浸润深度、淋巴结转移、临床分期有关,Spearman相关系数分别为0.360(P=0.005)、0.321(P=0.012)、0.412 (P=0.001)。Her-2/Neu表达阳性的患者无病生存期及中位生存期均显著低于表达阴性者。3.Ki-67的表达与浸润深度、临床分期有关,Spearman相关系数分别为0.269 (P=0.038)、0.265(P=0.041), Ki-67表达阳性的患者无病生存期及中位生存期均显著低于表达阴性者。4.Her-2/Neu及Ki-67共表达阳性与临床分期有关,Spearman相关系数为0.311(P=0.016), Her-2/Neu及Ki-67共表达阳性患者的中位生存期显著低于共表达阴性者。5.胃癌患者的Her-2/Neu与Ki-67的表达呈正相关,r=0.402,P值为0.001,有统计学意义。结论:1.Her-2/Neu的表达与肿瘤浸润深度、淋巴结转移情况及TNM分期相关;Ki-67的表达与肿瘤浸润深度及TNM分期相关。二者在胃癌中均阳性表达,与组织学类型无关。生存分析显示,Her-2/Neu、Ki-67阳性表达者生存期劣于阴性表达者。2.Her-2/Neu与Ki-67在胃癌中表达呈正相关,二者共表达与肿瘤的TNM分期相关;共表达阳性患者生存期劣于共表达阴性患者。更多还原

【Abstract】 Background: Gastric carcinoma is one of the most common malignant tumor threatening people’s health in China. Most patients are diagnosed at advanced stage,with poor prognosis and short survival. The health of people is seriously impacted by gastric carcinoma. Therefore, the factors associated with prognosis have been concerned inclinical work.The incidence and development of gastric carcinoma related to the variation of multiple genes and multiple protein. Her-2/Neu is a protooncogene. Her- 2/Neu protein is a transmembrane glycoprotein with activity of receptor-tyrosine kinase.Her-2/Neu can start the signal transduction system which is regulated by the tyrosine kinase .Ki-67 is a nonhistone , nucleoprotein, related to mitosis, and is widely used for assessment of tumor cell proliferation.The purpose of the study is to explore the expression of Her-2/Neu and Ki-67 in different gastric carcinoma tissues. Analyze their correlation with the clinicopathological features and prognosis. To guide clinical treatment and assessment of prognosis .Objective: To exam the expression of Her-2/Neu and Ki-67 in different gastric carcinoma tissues. To analyze the correlation between both protein and the impact on the clinicopathological features and on the survival of gastric carcinoma .Methods: The immunohistochemical staining was used to detected the expression of Her-2/Neu and ki-67 in 60 cases of gastric carcinoma. Comprehensive analysis was carried out through combining with the clinicopathological features and the datas from following up of the patients. The Chi-square test and Fisher exact propability have used to analyze whether the expression of Her-2/Neu and ki-67 is different in various types of gastric carcinoma tissues.The method of Spearman was used to analyze the correlation between the expression of independent or coexpression at both protein and clinicopathological features. Kaplan-Meier method and Log-rank test were used to analyze the impact of copositive expression of both protein on the survival time including disease-free survival time and overall survival time on.Results:1. In the 60 cases of gastric carcinoma,the positive expression rate of Her-2/Neu was 48.3% ,the positive expression rate of Ki-67 was 65%.No difference were observed in their expression on various types of gastric carcinoma tissues.2.The expression of Her-2/Neu was positively correlated with depth of invasion, lymph node metastasis and TNM stage.The coefficient correlation of Spearman are 0.360(P=0.005)、0.321(P=0.012)、0.412 (P=0.001). Her-2/Neu positive patients had significantly lower survival time which include disease-free survival time and the median survival time than Her-2/Neu negative patients (P<0.05).3. The expression of Ki-67 was positively correlated with depth of invasion and TNM stage.The coefficient correlation of Spearman are 0.269 (P=0.038)、0.265(P=0.041), Ki-67 positive patients had significantly lower survival time which include disease-free survival time and the median survival time than that of Ki-67 negative patients (P<0.05).4. Co-positive expression of Her-2/Neu and Ki-67 was correlated with TNM stage.Both positive patients had lower survival time than of co-negative patients (P<0.05).5. There was a positive relationship between the expression of Her-2/Neu and Ki-67(P = 0.001, r = 0.402),. Which is statistically significant.Conclusion:1. The expression of Her-2/Neu was positively correlated with depth of invasion, lymph node metastasis and TNM stage. The expression of Ki-67 was positively correlated with depth of invasion and TNM stage. Both Her-2/Neu and Ki-67 are positively expressed in gastric carcinoma,but their expression has no correlation with histological type . Results from the survival analysis showed that the patients with Her-2/Neu or Ki-67 positive expression had lower survival time than patients with negative expression.2. There was a positive correlation between the expression of Her-2/Neu and Ki-67. Co-positive expression of Her-2/Neu and Ki-67 was correlated with TNM stage.Co-positive patients with co-positive expression of Her-2/Neu and Ki-67 had lower survival time than patients with co-negative expression.更多还原