【作者】 郝曙光；

【导师】 冯笑山；

【作者基本信息】 河南科技大学 ， 肿瘤学， 2010， 硕士

【摘要】 目的:检测贲门肠上皮化生组织及贲门各级病变组织中Ki67、DAS-1及TFF3蛋白的表达变化,探讨不同亚型贲门肠上皮化生与贲门癌的相关性。方法:收集河南省林州地区无症状人群胃镜普查贲门组织以及贲门癌手术标本共计170例。分为3组:贲门炎组织25例、肠化组织80例(包括无癌肠化组织15例,癌旁肠化组织65例)及贲门癌组织65例。采用免疫组织化学SP法,分别检测各组组织中Ki67、DAS-1及TFF3蛋白的表达情况;利用SPSS软件分析各组间Ki67、DAS-1及TFF3蛋白表达的差异。并采用粘液组织化学染色的方法对80例肠化组织进行分型,分析肠化亚型与贲门癌之间的相关性。结果:在贲门炎、肠化组织及癌变组织中,Ki67蛋白阳性表达率分别为16.0%、43.8%和53.8%,经统计学分析Ki67蛋白表达在各组间的表达差异具有统计学意义,并与贲门炎组织、肠化、再至癌变这一病理变化过程呈正相关(r=0.436,P<0.05)。通过粘液组化染色分型,Ⅰ型、Ⅱ型、Ⅲ型在门诊胃镜活检无癌肠化组织及贲门癌癌旁肠化组织中所占比例分别为66.7%、20.0%、13.3%和13.8%、30.8%、55.4%,经统计学分析Ⅲ型贲门肠化在贲门癌癌旁肠化组织中所占的比例55.4%显著高于门诊胃镜活检无癌肠化组织13.3% (χ2=39.305,P <0.01)。DAS-1蛋白、TFF3蛋白在贲门炎、肠化组织及癌变组织中的阳性表达率分别为0%、38.8%、53.8%和24%、65%和53.8%,经统计学分析DAS-1蛋白在各组间的表达差异具有统计学意义,并与贲门组织的病理变化呈正相关(r=0.572,P<0.05);TFF3蛋白在贲门炎、肠化组织两组间的表达具有统计学意义(χ2=34.031,P<0.05),在肠化组织、癌组织两组间的表达无统计学意义(χ2=2.512,P>0.05)。在Ⅰ型、Ⅱ型和Ⅲ型贲门肠化组织中,DAS-1蛋白、TFF3蛋白的阳性表达率分别为0%、17.4%、71.1%和68.4%、78.4%、55.3%,经统计学分析DAS-1蛋白在各组间的表达具有明显差异,其中Ⅲ型显著高于Ⅰ型(χ2=110.078,P<0.01),TFF3蛋白在各组间的表达无统计学意义(χ2=12.033,P>0.05)。从形态学上分析,TFF3蛋白在贲门炎及Ⅰ型肠化组织中主要表达在柱状细胞的纹状缘,Ⅲ型肠化及癌变组织中主要表达在细胞质中,其表达的位点与病理类型相关(Kappa=0.490)。结论:1、Ki67蛋白在贲门炎、肠化组织及癌变组织中表达率逐渐增高,表明随着组织学形态的改变,细胞的增殖能力逐渐增强。提示贲门肠上皮化生是贲门癌变过程中一个重要环节。2、DAS-1蛋白在贲门炎、肠化组织及癌变组织中的表达差异具有统计学意义,提示该蛋白有可能成为提高贲门癌早期诊断率的监测指标及预警分子。3、伴DAS-1过表达的Ⅲ型贲门肠化与贲门癌的关系密切,可能是河南贲门癌高发区GCA的一种重要的癌前病变。4、TFF3蛋白在贲门炎及Ⅰ型肠化组织中主要表达在柱状细胞的纹状缘,Ⅲ型肠化及癌变组织中主要表达在细胞质中,其表达位点的转变可能说明了该蛋白表现为抑癌和促癌两种不同作用的结构基础。更多还原

【Abstract】 Objective: To identify the relationship between subtypes of cardia intestinal metaplasia and gastric cardia adenocarcinoma by analyzing the expression of Ki67, das-1 and TFF3 proteins in subtypes of cardia intestinal metaplasia and cardia lesions at all levels.Methods: One hundred and seventy cases of cardia tissues by gastroscope and carida cancer tissues by surgery were collected in Linzhou area of Henan province. immunohistochemical S-P method has been employed to examine the expression of Ki67, das-1 and TFF3 proteins in 25 gastric cardia hilitis, 15 intestinal metaplasia without cancer, 65 intestinal metaplasia adjacent cancer 65 gastric cardia adenocarcinoma issue specimens. Eighty intestinal metaplasia issue specimens were typed by the Mucus staining method. The relationship between subtypes of cardia intestinal metaplasia and gastric cardia adenocarcinoma was analyzed by SPSS soft.Results: The positive rates of Ki67 protein in gastric cardia hilitis, intestinal metaplasia, and carcinoma tissues were 16.0%, 43.8%, and 53.8%, respectively. Statistical analysis using chi-square showed the expression level of Ki67 protein was different and correlated well with the pathological grading of the lesions (r=0.436, P<0.05). Eighty cases of gastric cardia intestinal metaplasia were classified three types by mucosal staining. The proportion of typeⅢIM was significantly higher for IM foci in tissues adjacent to GCA (55.4%) than in gastric cardia biopsy tissues with IM from the outpatient (13.3%) (P<0.01). The positive rates of DAS-1 protein and TFF3 protein in gastric cardia hilitis, intestinal metaplasia, and carcinoma tissues were 0%, 38.8%, 53.8%, and 24%, 65%, 53.8% respectively. Statistical analysis using chi-square showed the expression level of DAS-1 protein was different and correlated well with the pathological grading of the lesions (r=0.572, P<0.05). For TFF3 protein, statistical significance of the positive rates was showed only between cardia hilitis and intestinal metaplasia(χ2=34.031, P<0.05). Among three types of intestinal metaplasia, The positive rates of DAS-1 and TFF3 were 0%, 17.4%, 71.1% and 68.4%, 78.4%, 55.3% respectively. The positive rates of DAS-1 in IM increased gradually from typeⅠto typeⅢ(χ2=110.078,P<0.01), and TFF3 protein expression was not statistically significant(χ2=12.033, P>0.05). In the cardia inflammation and intestinal metaplasia tissues, TFF3 protein was mainly expressed striated border in columnar cells while Intestinal metaplasia with dysplasia and cancerous tissue, mainly expressed in the cytoplasm. The location of TFF3 expression correlated with the pathological types (Kappa=0.490).Conclusion: It is cardia intestinal metaplasia that prompted the course of carcinoma. It is because that the position rates of Ki67 protein in gastric cardia hilitis, intestinal metaplasia and cancerous tissue increased gradually, which indicated that the ability of cell differentiation reduced gradually with the histological changes gradually. Expression difference of Das-1 protein in the levels of gastric cardia tissues was involved in gastric cardia carcinogenesis and it could potentially become the important risk factors in detecting GCA. Furthermore, The typeⅢIM with over-expression of DAS-1 is closely related to GCA, which could potentially become one of important precancerous lesions for GCA at the high-incidence areas in Henan province. The transition in the location of TFF3 expression showed that the double role of TFF3 depends on its different expression location.更多还原