【作者】 华晨；

【导师】 陈丽荣；

【作者基本信息】 浙江大学 ， 肿瘤学， 2004， 硕士

【摘要】 【目的】 胃癌是我国常见恶性肿瘤之一，其发病机制仍然不很清楚。错配修复基因和凋亡相关基因参与了人体恶性肿瘤的发生、发展。本研究的目的是分析错配修复基因Msh2和凋亡相关基因bcl-2、bax在胃癌组织中的表达，并探讨它们的表达相关性以及与胃癌临床病理因素和预后的关系。 【方法】 收集1989—1994年间由浙江大学医学院附属二院诊治的有随访资料的63例胃癌石蜡包埋标本。用免疫组化法检测胃癌组织中Msh2、bcl-2和bax蛋白的表达水平。比较三种蛋白表达水平与胃癌临床病理因素的关系，以及与术后生存率的关系。比较Msh2、bcl-2和bax在胃癌中表达的相关性。对临床病理指标、Msh2、bcl-2、bax蛋白表达情况与预后的关系进行多因素分析。所有数据用SPSS for windows 10.0软件包进行统计分析。样本率的比较用卡方检验和四格表精确概率法。计量资料多组比较采用单因素方差分析One-Way ANOVA法。双向有序分类计数资料关联性采用Kendall tau等级资料相关分析法。生存率分析采用浙江大学医学院硕士(肿瘤学)学位论文摘要一一中文2(刃4 05Kaplan一Meier法及Log一rallk检验完成，多因素回归分析用Cox比例风险模型完成。以p毛0.05为有统计学意义。t结果】l各临床病理因素对患者术后生存率的影响 下NM分期与患者五年生存率显著相关‘p<0.05)，分期晚的病人预后差。年龄、性别、Lauren分型、分化程度与术后五年生存率无显著相关性。2 bel一2、bax、MshZ蛋白免疫组化结果 在63例胃癌石蜡包埋标本中，bcl一2、bax和Ms眨蛋白表达的总阳性率分别为75%、47/63)、73%(46/63)、49%(31/63)。男性患者bel一2蛋白显著高于女性患者切<0.05)，bax蛋白阳性表达率在男性或Lauren分型为肠型的胃癌病人中显著增高(p<0.01)，MshZ蛋白表达情况在各临床病理因素中差别无显著性意义 (p>0.05)。bel一2呈不同强度等级表达时，患者术后生存率差别无显著性意义 (P>o.05)。bax弱表达组生存率较强表达组显著增高(广0.05)，且当生存日数大于1000天后，bax强表达组患者生存率明显降低。MshZ不同表达水平与术后五年生存率之间无显著性差异(p>。.05)。3 bel一2、bax、MshZ蛋白表达的相关性分析 bax与bcl一2表达具有显著相关性(p<0.05)。结合资料可认为随着bel一2表达阳性率的增高bax表达阳性率逐步增高。bax表达与MshZ表达具有显著的相关性(P<0.05)。结合资料可以认为，随着bax表达阳性的逐步增强，MshZ表达逐步增高。bel一2与MshZ表达之间无显著相关性(p>0.05)。当MshZ表达为一、+、料、料+时，bel一2表达分数的均数分别为5.84、5.42、5.00、5.50，各等级表达分数差别无显著性差异(P>0.05)。但由二次方程拟合成曲线后可见，随MshZ表达等级的提高，bcl一2表达分数有逐步降低的趋势。4 Cox风险比例模型的建立 肿瘤的TNM分期、Lauren分型和MshZ表达是胃癌中具有独立预后意义的指标。根据Cox模型中有独立预后意义的指标建立评分标准，预后指数范围从5 一10分不等，预测术后5年生存率从100%一0%不等。随预后指数的增加，术后5年生存率逐渐下降，趋势检验有极显著的统计学意义伽<0.01)。按预后指数 分组，评分5一7分组的患者术后5年生存率为83%，预后较好，评分8一10分浙江大学医学院硕士(肿瘤学)学位论文摘要一一中文200405组的患者术后5年生存率为30%，预后差，两组之间差别有极显著性意义沙<0 .01)。【结论】l在男性胃癌患者中，bel一2和bax蛋白表达水平高于女性，bax蛋白在肠型胃 癌中表达较高。单项bel一2和bax的表达状况无预后判断意义。Zbc卜2蛋白表达与bax蛋白表达之间和MshZ蛋白表达与bax蛋白表达之间均 存在显著相关性。三者同时检测有助于了解肿瘤细胞凋亡状态及预后的判 断。3多因素分析表明，胃癌下 NM分期、Lauren分型、MshZ蛋白表达情况是具有 独立意义的预后指标。根据Cox风险比例模型建立风险评分标准，提示预后 指数达到7分以上者术后生存率显著降低。更多还原

【Abstract】 [Objictive]Gastric carcinoma is one of the most common malignancies in our nation. It is not entirely clear for the pathogenesis of gastric carcinoma. DNA mismatch repair genes and apoptosis-associated genes are involved in the histogenesis and development of human malignancies. In the present study, expression of Msh2, bcl-2 and bax in gastric carcinoma was investigated. The relationship of Msh2 expression to bcl-2 and bax in gastric carcinoma was analysed. The association of their expression with clinical pathological factors and prognosis outcome was explored.[Methods]63 specimens of gastric carcinoma with well-controlled follow up from 1989 - 1994 year were obtained from the Second Affiliated Hospital of Zhejiang University School of Medcine. Immunohistochemistry was carried out to detect the expression of bcl-2 bax and Msh2. The relationship among them was analysed with chi-square test and kendall tau correlation test by SPSS for Windows 10.0 software. With Kaplan-Meier method , Log-rank test and Cox proportional-hazards model, we achieved the survival rate results of computerized analysis of gastric carcinoma. [Results]1 Effect of clinicopathologic characters upon survival rates of patients with gastric carcinomaTNM grade had obvious relation to survival rate(p<0.05). Patient ages at diagnosis , gender the degrade of differentiation , and the typing of Lauren had no obvious relation to prognosis(p>0.05).2 Immunohistochemistry of bcl-2 bax and Msh2 protein.In 63 specimens of gastric carcinoma the positive rate of bcl-2,bax and Msh2 was 75 % ( 47/63 ), 73 % ( 46/63 ), 49 % ( 31/63 ) respectively. The expression level of bcl-2 in male patients was significantly higher than that in female (p<0.05). The expression level of bax in male patients and Lauren’ I type was significantly higher than that in female andLauren’ II type (p<0.01). The expression level of Msh2 had no significant relation to clinicopathologic characters of gastric carcinoma. No significant difference of survival rate was observed when bcl-2 or Msh2 expressed in different level(p>0.05). The survival rate in bax low expression group was higher than that in the high group(p=0.05), and when surviving days of patients with gastric carcinoma were over 1000 days ,survival rates in the bax high expression group had obviously descended.3 The relationship among bcl-2 , bax and Msh2 expressionThere was significant relationship between bax and bcl-2 expression(p<0.05). When the expression level of bax was higher , the level of bcl-2 was higher too. The relationship between bax and Msh2 expression existed in gastric carcinoma(p<0.05). No significant relationship between bcl-2 and Msh2 expression was observed(p>0.05). When Msh2 expression level was negative, mild positive moderate positive and strong positive , the expression value of bcl-2 was 5.84 5.42, 5.00, 5.50(p>0.05). But with the quadratic curve we found that higher the Msh2 expression was ,lower the bcl-2 was.4 The Cox proportional-hazards modelIn Cox model TNM stages, Lauren type and expression of Msh2 were independent risk factors. According to the relative risk of TNM stages, Lauren type, Msh2 expression in Cox model , we established aprognostic index. The range of prognostic index was 5-10 , 5 year survival rate varied from 100 - 0% , and there was trend of decline in survival rate when the prognostic index was increased(p<0.01). The 5-year survival rate of patients scored 5 - 7 was 83% , that of patients scored 8 - 10 was 30%(p<0.01). [Conclusions]1 bcl-2 and bax expression level are higher in male patients with grastric carcinoma than those in female. Bax expression level is higher in Lauren type I than that in Lauren type II. We can not estimate prognosis with bcl-2 or bax isolatively.2 There are significant correlation between bax and bcl-2 exoression , or between bax and Msh2 expression. Their expression level in gastri更多还原