应用组织芯片和荧光原位杂交技术检测乳腺癌组织中HER-2/neu基因扩增及其蛋白产物的表达  

HER -2/neu gene amplification and protein expression by fluorescence in situ hybridization analysis with a tissue microarray

作　　者：刘庆猛[1] 何平生[1] 谭卫峰[1] 张再洋[2] 

机构地区：[1]绍兴第二医院病理科,浙江绍兴312000 [2]绍兴第二医院肿瘤外科,浙江绍兴312000

出　　处：《肿瘤》2013年第8期711-716,共6页Tumor

基　　金：浙江省医药卫生科学研究基金(编号:2007B217)

摘　　要：目的:探讨乳腺癌组织中人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2/neu)基因扩增与其蛋白产物C-erbB-2表达之间的相关性,并评价应用组织芯片进行荧光原位杂交(luorescencein situ hybridization,FISH)检测HER-2/neu基因扩增的临床应用价值。方法:收集80例乳腺癌组织制备芯片,以10例乳腺良性病变周围正常乳腺组织为对照组,分别进行FISH和免疫组织化学(immunohistochemistry,IHC)检测乳腺癌组织中HER-2/neu基因扩增及C-erbB-2蛋白的表达情况。结果:80例乳腺癌组织中,FISH法检测结果显示,有18例样品存在HER-2/neu基因扩增,阳性率为22.5%(18/80);IHC法检测结果提示,C-erbB-2蛋白强阳性(+++)表达的组织中HER-2/neu基因阳性率为90.9%(10/11),中等强度阳性(++)表达的组织中阳性率为66.7%(4/6),阴性或弱阳性(0/+)表达的组织中基因扩增的阳性率仅为6.3%(4/63)。在浸润性导管癌Ⅰ级中HER-2/neu基因扩增的阳性率为10.0%(2/20),Ⅱ级中为23.3%(7/30),Ⅲ级中为30.0%(9/30)。10例正常乳腺对照组织中均未检测到HER-2/neu基因扩增及C-erbB-2蛋白的表达。统计结果显示,C-erbB-2蛋白强阳性(+++)和中等强度阳性(++)表达者HER-2/neu基因扩增的阳性率显著高于C-erbB-2蛋白阴性或弱阳性表达者,差异有统计学意义(P<0.01);HER-2/neu基因扩增的阳性率随组织学分级的提高而升高。IHC法检测C-erbB-2蛋白的表达与FISH法检测HER-2/neu基因扩增有较高的一致性(Kappa=0.746,P<0.05),但C-erbB-2蛋白的表达仍有一定比例的假阳性或假阴性。结论:乳腺癌组织HER-2/neu基因扩增与C-erbB-2蛋白的过表达密切相关并与组织学分级有关。FISH法检测HER-2/neu基因状态比C-erbB-2蛋白的表达更客观和可靠,C-erbB-2蛋白的检测可作为初筛手段。应用组织芯片进行FISH法检测结果可靠,具有实用、高效和经济的优点,对于大样本的研究具有优势。Objective： To investigate the correlation between HER-2 （human epidermal growth factor receptor-2）/neu gene amplification and the expression of C-erbB-2 protein in human breast cancer,and to evaluate the value of FISH （fluorescence in situ hybridization） analysis with a tissue microarray in clinical application.Methods： A series of 80 specimens of breast cancer and 10 control specimens of normal breast tissues adjacent to benign breast lesion were collected.The FISH analysis with a tissue microarray was performed.The amplification of HER -2/neu gene and the expression of C-erbB-2 protein in breast cancer tissues were detected by IHC （immunohistochemistry） and FISH,respectively.Results： In 80 breast cancer tissue specimens,HER -2/neu gene amplification was detectable in 18 specimens with a positive rate of 22.5% （18/80） by FISH.The positive rates of HER -2/neu gene amplification in breast cancer tissues with strong （＋＋＋）,moderate （＋＋） and weak/negative （＋/0） expressions of C-erbB-2were 90.9% （10/11）,66.7% （4/6） and 6.3% （4/63）,respectively.The positive rates of HER -2/neu gene amplification in gradesⅠ,Ⅱ and Ⅲ invasive ductal carcinoma were 10.0% （2/20）,23.3% （7/30） and 30.0% （9/30）,respectively.The positive rates of HER -2/neu gene amplification in breast cancer tissues with strong （＋＋＋） and moderate （＋＋） expressions of C-erbB-2 were higher than that in the breast cancer tissues with weak/negative （＋/0） expression of C-erbB-2 （P〈0.01）,and this positive rate was increased with the histological grade elevated.The result of IHC revealed that there was a consistence between the HER-2/neu gene amplification and C-erbB-2 protein expression （Kappa = 0.746,P〈0.05）,but a certain false-positive or false-negative rate of C-erbB-2 protein expression was observed.Conclusion： There is a close relationship between HER -2/neu gene amplification and C-erbB-2 protein overexpression in human breast cancer.It’s more obj

关 键 词：乳腺肿瘤 受体 erbB-2 原位杂交 荧光 芯片分析技术 

分 类 号：R737.9[医药卫生—肿瘤]