宫颈鳞癌论文：宫颈鳞癌中HPV、HER-2、EGFR及Ki67的表达

宫颈鳞癌论文：宫颈鳞癌中HPV、HER-2、EGFR及Ki67的达 宫颈鳞癌论文:宫颈鳞癌中HPV、HER-2、EGFR及Ki67的表达 【中文摘要】1探讨HPV和HER2基因以及CerBb2、EGFR、Ki67蛋白在宫颈鳞状上皮癌变过程中表达，它们之间及与临床病理参数的相关性。2免疫组织化学(IHC)与荧光原位杂交(FISH)检测宫颈鳞癌组织HER2基因状态及蛋白的一致性，并评估其临床价值。方法: 1收集60例宫颈鳞癌、61例CIN及21例正常宫颈组织标本，应用组织微阵列法制作组织芯片。2荧光原位杂交法(FISH)检测宫颈鳞癌、CIN及正常宫颈组织中HER2的基因状态。。3显色原位杂交法(CISH)检测宫颈鳞癌、CIN及正常宫颈组织中HPV的基因状态。4免疫组织化学Envision二步法分析宫颈鳞癌、CIN及正常宫颈组织中CerBb2、EGFR、Ki67的表达。结果:1荧光原位杂交(FISH)检测HER2基因状况检测60例宫颈鳞癌标本，13例有基因扩增，扩增率为21.67%;30例CIN?级标本，1例发生基因扩增，扩增率为3.33%;CIN?~?级和正常宫颈组织均无扩增。在没有发生扩增的病例中有7例17号染色体多体。2 HPV DNA(CISH)在宫颈癌变过程中的基因状态检测宫颈正常组织、CIN?~?、CIN?及鳞癌中，HPV16/18的阳性率分别为0%、9.7%、46.7%、和71.7%，各组间差异有显著性(P<0.05)，宫颈鳞癌中HPV16/18 DNA阳性率与分化程度、分期及淋巴结转移无相关关系。3 CerbB2、EGFR、Ki67蛋白在宫颈鳞状上皮癌变过程中的 表达检测从宫颈正常鳞状上皮、CIN到鳞癌的发展过程中HER2、EGFR与Ki67蛋白的表达率逐渐增高(P<0.05)。CerbB2蛋白在三组的阳性表达率依次为0.00%,6.56%,31.67%。EGFR在三组中的表达率依次为0.00%，54.10%，71.67%。Ki67在三组中的表达率依次为0.00%，49.18%，85.00%。CerbB2与Ki67的表达分别与宫颈鳞癌的分级、分期及淋巴结转移密切相关(P<0.05)，分级和分期越高，表达阳性率越高，淋巴结转移者比未转移者CerbB2与Ki67的表达阳性率高，EGFR的表达与宫颈鳞癌的分期与淋巴结转移密切相关(P<0.05)，分期越高，EGFR阳性表达越多，淋巴结转移者比未转移者EGFR的阳性表达率高;与宫颈鳞癌的分级无相关关系(P>0.05)。4比较荧光原位杂交(FISH)法与免疫组织化学(IHC)法检测宫颈鳞癌中HER2基因的扩增与其蛋白CerbB2的表达。宫颈鳞癌中，检测到CerbB2蛋白表达(+++)者1例和表达(++)者12例，其中只有1例(++)者未扩增;表达(+)者6例，其中1例显示扩增,5例未扩增。CIN?级中，CerbB2蛋白表达(++)者2例，1例扩增;表达(+)者2例，均无扩增。CIN?~?级组中，免疫组化技术与FISH技术均无阳性表达。结论:1 EGFR、Ki67的表达与宫颈鳞癌的发生发展密切相关。2、HPV感染是宫颈鳞癌的触发因素之一。3、HER2基因扩增与蛋白表达可能参与调控了宫颈鳞癌的发生发展过程。4、宫颈鳞癌HER2基因扩增与蛋白检测，具有较好的一致性。 【英文摘要】1. To investigate the expression of HPV,HER2,EGFR and Ki67 in the cervical squamousintraepithelial canceration course,analyze the correlation between the expression and clinicalpathological parameters, and analyze the correlation of the four gene.2.Through the comparison of HER2 protein/gene status detected byimmunohistochemistry(IHC), Fluorescent in-situ hybridization(CISH), to explore the clinicalsignificance of IHC and FISH on detecting HER2 gene status.Methods1. Collecting 60 cases of the squamous cell cervical carcinoma,61 cases of the cervicalintraepithelial neoplasia and 21 cases of the normal cervical intraepithelial.Tissue microarraywas made by Tissue microarray technology.2. Envision immunohistochemisty method was performed to analyze the expression ofEGFR,CerbB2 and Ki67 in the squamous cell cervical carcinoma,CIN and the normal.3. CISH was performed to analyze the gene Status of HPV in the squamous cell cervicalcarcinoma,CIN and the normal.4. FISH was performed to analyze the HER2 gene status in the squamous cell cervicalcarcinoma,CIN and the normal.Results1. The expression of CerbB2,EGFR,Ki67 in the cervical squamous intraepithelialcanceration course.The positive expression rates of CerbB2,EGFR and Ki67 display a improving trend fromthe normal cervical intraepithelial,the intraepithelial neoplasia to carcinoma(P<0.05). In theabove three groups，the positive expression rates of CerbB2 were 0.00%,6.56%,31.67%,EGFRwere 0.00%,54.10%,71.67%,and Ki67 were 0.00%,49.18%,85.00%.The expression of CerbB2and Ki67 was closely related to the stage ,degree of differentiation and metastasis of lymphnode in the squamous cell cervical carcinoma(P<0.05).The expression of EGFR was related tothe stage and metastasis of lymph node(P<0.05),there was no relationship between it and thedegree of differentiation.2. The gene status of HPV detected by CISH in the cervical squamous intraepithelial canceration course.In the normal cervical intraepithelial,CIN?~?, CIN ?and the carcinoma,the positiveexpression rates of HPV were 0%,9.7%,46.7%,71.7%,there were significant differences amongthe four groups(P<0.05).It was not related to the stage ,degree of differentiation and metastasisof lymph node in the squamous cell cervical carcinoma(P>0.05).3. The gene status of HER2 detected by FISH.Among the 60 carcinoma cases,there were 13 cases having gene amplification, 2 of whichhad chromosome 17 polysomy. There was only 1 case having amplification in the 30 CIN?cases.There was no gene amplification in the both CIN?~?and normal.4. Comparison of HER2 protein/gene status detected by IHC, FISH.In the carcinoma ,among the 1 case expressing (+++) and the 12 cases expressing (++) byIHC,there was only 1 case expressing (++) without gene amplification,in the 6 cases expressing(+),only 1 case amplified.In the CIN?,there was 1 case amplified in the 2 cases expressing(++);the 2 cases expressing (+) were not amplifying.In the CIN?~?,there was no expressingin both IHC and FISH.Conclusion1. The expressing of EGFR and Ki67 is closely related to the occurrence and developmentof the squamous cell cervical carcinoma.The infection of HPV is one of the triggers for thesquamous cell cervical carcinoma.The expression and the amplification of HER2 maybe takepart in the regulation of the squamous cell cervical carcinoma.2. In the detecting of HER2,there is good consistence between IHC and FISH in the casesexpressing (++~+++) by IHC. 【关键词】宫颈鳞癌 上皮内瘤变 免疫组织化学法 显色原位杂 交法 荧光原位杂交法 HPV HER2 EGFR Ki67 【英文关键词】CSCC CIN IHC CISH FISH HPV HER2 EGFR Ki67 【目录】宫颈鳞癌中HPV、HER-2、EGFR及Ki67的表达 摘要 5-7 Abstract 7-8 英文缩略词 9-10 前言 10-11 与方法 11-15 结果 15-19 讨论 19-22 结论 22-23 参考文献 23-25 附图 25-31 综述 31-38 参考文献 35-38 个人简介 38-39 致谢 39