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1、【关键词】EB病毒相关胃癌 HER2 基因扩增 蛋白表达 胃癌 表皮生长因子受体家族 HER3 病理 临床 预后【英文关键词】Epstein-Barr virus associated gastric carcinoma HER2 geneamplification protein expressiongastric cancer HER family HER3 pathology clinicalEB病毒相关胃癌论文：胃癌中HER2基因扩增及HER家族蛋白表达的临床病理意义【中文摘要】本课题分为以下二部分：第一部分EB病毒相关胃癌中HER2蛋白表达及基因扩增检测EB病毒相关胃癌（EBVaGC
2、）与EB病毒非相关胃癌（EBVnGC）中HER2蛋白表达及基因扩增情况，初步探讨它们在两种胃癌中差别的原因。1运用免疫组化方法检测EBVaGC及EBVnGC中HER2蛋白表达水平，分析两种胃癌中HER2蛋白表达率及过表达率的差别。2采用荧光原位杂交方法检测EBVaGC及EBVnG中HER2基因有无扩增，分析两种胃癌中HER2基因扩增率的差别。1EBVaGC及EBVnGC中HER2蛋白均存在不同程度的表达及过表达，EBVaGC中HER2蛋白表达率及过表达率分别为24.4%（11/45）及6.67%（3/45），EBVnGC中HER2蛋白表达率及过表达率分别为68%（34/50）及28%（14/5
3、0），两种胃癌HER2蛋白表达率及过表达率均有显著差异（P0.001，P=0.007）。2EBVaGC及EBVnGC中均存在HER2基因扩增，EBVaGC中HER2基因扩增率为2.2%（1/45）, EBVnGC中HER2基因扩增率为18%（9/50），二者有显著差异（P=0.03）。3在EBVaGC及EBVnGC中，HER2免疫组化染色结果为0和1+的组织HER2基因均无扩增，HER2免疫组化染色结果为3+的组织HER2基因均有扩增。EBVaGC组织中HER2蛋白表达率、过表达率及HER2基因扩增率较EBVnGC组织均显著降低。第二部分胃癌中HER家族蛋白表达及过表达的临床病理意义通过检测人
4、类表皮生长因子受体家族（HERs）蛋白在胃癌组织中的表达，探讨HER家族蛋白表达、过表达、联合表达及联合过表达与胃癌临床病理特征及预后之间的关系。采用免疫组织化学法检测124例手术切除的胃癌组织中HER家族蛋白的表达，分析HER家族蛋白表达、过表达、联合表达及联合过表达与胃癌临床病理特征和预后之间的关系。1124例胃癌中HER家族蛋白HER1、HER2、HER3、HER4的表达率分别为41.1%（51/124）、59.7%（74/124）、82.2%（102/124）、28.2%（35/124）；其过表达率分别为6.5%（8/124）、26.6%（33/124）、22.6%（28/124）、1
5、2.1%（15/124）；癌旁非肿瘤胃粘膜均未见HER家族蛋白表达。2肠型胃癌中HRE2蛋白过表达较弥漫型胃癌更常见（P=0.001）。3HER3过表达的胃癌常浸润深度更深、淋巴结转移、远处转移、TNM分期更晚及预后更差。（P均0.05）；HER1、HER2和HER3联合表达与胃癌远处转移有关（P=0.035）。HER家族中HER3过表达可以作为评估胃癌恶性生物学行为的指标。【英文摘要】The paper includes two parts as follows:The first partHER2protein expression and HER2gene amplification i
6、n EBVaGC【s】To detect the expression of HER2protein and HER2gene copy number inEBVaGC and EBVnGC, and discuss the diffirences between these two kinds ofgastric carcinoma.【Methods】1. The expression of HER2protein and HER2gene copy number weredetermined by immunohistochemistry and FSIH in45cases of EBV
7、aGC and50casesof EBVnGC.2. To discuss the differences of rates of HER2protein expression, overexpressionand HER2gene amplification between EBVaGC and EBVnGC. 【Results】1. In EBVaGC,the rates of HER2protein expression and overexpression were24.4%(11/45) and6.67%(3/45), respectively; In EBVnGC, the rat
8、es of HER2proteinexpression and overexpression were68%(34/50) and28%(14/50), respectively; therates of HER2protein expression and overexpression were obviousely decreased inEBVaGC (P 0.001, P=0.007).2. HER2gene was amplified in EBVaGC and EBVnGC, the rates of HER2geneamplification were2.2%(1/45) and
9、18%(9/50), respectively. The rates of HER2geneamplification were obviousely decreased in EBVaGC (P=0.007).3. In EBVaGC and EBVnGC, all the grade of “0” and “1+” in IHC were negativein FISH, and all the grade of “3+” in IHC were positive in FISH.【Conclusions】The rates of HER2protein expression, overe
10、xpression and HER2geneamplification were obviousely decreasede in EBVaGC. The second partThe clinicalpathological significance of expression andoverexpression of HER family proteins in gastric carcinoma【s】To investigate the correlation of expression, overexpression, co-expression andco-overexpressio
11、n of HER family proteins with the clinicopathological parameters ofgastric cancer.【Methods】Expression of HER1-4proteins were determined by immunohistochemistry in124gastric cancer tissues, the correlation of expression, overexpression,co-expression and co-overexpression of HER family proteins with c
12、linicopathological parameters and prognosis of the patients were also analyzed.【Results】1. The expression rates of HER family proteins in124gastric cancer were41.1%(51/124),59.7%(74/124),82.2%(102/124) and28.2%(35/124), respectively.2. The overexpression rates of HER1-4proteins in the patients with
13、gastriccancer were6.5%(8/124),26.6%(33/124),22.6%(28/124), and12.1%(15/124),respectively.3. HER2overexpression was associated with intestinal-type gastric cancer(P=0.001).4. HER3overexpression was associated with depth of invasion, lymph nodemetastasis, distant metastasis, TNM stage of gastric cance
14、r and worse survival(P0.05); the co-expression of HER1, HER2and HER3were associated with distantmetastasis of gastric cancer (P=0.035).【Conclusions】Overexpression of HER3may be used to assess the malignant biologicalbehavior and prognosis of gastric cancer.【目录】胃癌中HER2基因扩增及HER家族蛋白表达的临床病理意义中文摘要3-6ABSTRACT6-8目录9-10第一部分 EB 病毒胃癌中 HER2 蛋白表达及基因扩增10-23第1章 引言10-12第2章 材料与方法12-18第3章 结果18-20第4章 讨论20-22第5章 结论22-23第二部分 HER 家族在胃癌中表达及过表达的临床病理意义23-46第1章 引言23-26第2章 材料与方法26-31第3章 结果31-42第4章 讨论42-45第5章 结论45-46参考文献46-53中英文缩略词对照表53-54攻读学位期间的研究成果54-55致谢55