荧光原位杂交与免疫组化法检测乳腺癌HER-2表达的临床意义

[目的]探讨乳腺癌中荧光原位杂交(FISH)检测HER-2基因的扩增和免疫组织化学(IHC)检测HER-2蛋白表达在临床诊断及分子靶向治疗中的应用.[方法]采用FISH与IHC检测50例乳腺癌组织中HER-2基因的扩增与HER-2蛋白表达.[结果]50例浸润性乳腺癌中,FISH检测HER-2基因扩增阳性15例(30％),IHC检测HER-2蛋白表达(-～+)40例,HER-2蛋白表达(++)的2例,HER-2蛋白表达(+++)的8例.[结论] FISH检测HER-2基因的扩增与IHC检测HER-2蛋白表达(++-+++)有较高的一致性.对于IHC检测HER-2(-++)表达时,必须进一步FISH检测.     

荧光原位杂交与免疫组化对乳腺癌HER-2检测的对比研究

目的 探讨荧光原位杂交技术(FISH)检测石蜡标本乳腺癌HER-2基因和免疫组化法(IHC)检测HER-2蛋白表达的结果. 方法 采用荧光原位杂交技术(FISH)和免疫组化技术(IHC)分别检测203例乳腺癌患者手术切除标本的HER-2基因和HER-2蛋白表达,对两种方法检测结果进行对比分析.结果 203例HER-2 IHC结果阳性110例(54%),阴性93例(46%);FISH结果阳性60例(阳性率29%),阴性143例(71%).93例HER-2蛋白为阴性的患者中,HER-2基因表达阴性的87例,符合率93.6%(87/93);58例HER-2蛋白为+的患者中,HER-2基因表达为阳性的11例,符合率为19.0%(11/58);29例HER-2蛋白为++的患者中,HER-2基因表达为阳性的22例,符合率75.9%(22/29);23例HER-2蛋白为的患者中,HER-2基因表达为阳性的21例,两者符合率为91.3%(21/23).结论 对于IHC法初筛为阴性(-)或强阳性(+++)的患者两种方法检测的符合率(≥91.3%)较高,可选择性的进行FISH实验,尤其对于50岁以上年龄组的患者符合率(≥97.7%)更高,而对于IHC法初筛为阳性(+～++) 的患者应再进行FISH实验以确定HER-2基因的状态.     

FISH技术在乳腺癌Her2基因检测中的应用

目的:探讨乳腺癌中免疫组化法(IHC)检测cerbB2蛋白表达和荧光原位杂交法(FISH)检测Her2基因扩增,并评估其临床意义.方法:IHC及FISH法分别检测50例乳腺癌组织中cerbB2蛋白表达及Her2基因扩增状态,并进行分析比较.结果:50例乳腺癌中Her2蛋白表达(++)者21例中,17例出现Her2基因扩增(80.95%),4例无扩增;Her2蛋白表达(+++)者29例中,28例出现Her2基因扩增(96.55%),1例无扩增;50例乳腺癌中共有45例Her2基因扩增(90%),5例无扩增.两种方法的检测结果阳性率差异无统计学意义(P>0.05).结论:免疫组化检测Her2蛋白表达的情况可以傲为临床治疗的初筛,免疫组化检测Her2蛋白表达(++)及(+++)的病例需要进一步行Her2基因的扩增,来确定临床治疗方案.     

FISH在乳腺癌组织HER2/neu原癌基因检测上的应用及其临床意义的研究

目的对比研究乳腺癌中免疫组化法检测c-erbB2蛋白表达和荧光免疫原位杂交法(FISH)检测HER2基因扩增,并评估其临床价值。方法免疫组化染色法及FISH法分别检测42例乳腺癌组织中c-erbB2蛋白表达及HER2基因扩增状况,并进行对比分析。结果42例乳腺癌中c-erbB2蛋白表达( )者22例(52.38%),表达( )者20例(47.62%);42例乳腺癌中有20例(47.62%)出现HER2基因扩增,22例(52.38%)无扩增。两种方法的检测结果差异无统计学意义(P>0.05);但二者的吻合度一般,(k=0.430,P<0.05)。结论免疫组化可以作为临床治疗是否应用赫赛汀(Herceptin)的初筛,免疫组化呈阳性或强阳性的病例有必要进一步进行HER2基因扩增的检测,来确定临床治疗是否应用Herceptin,指导化疗药物的选择及判断患者的预后。     

荧光原位杂交法检测乳腺癌HER-2/neu表达及临床意义

目的探讨用荧光原位杂交(fluorescent in situ hybridization,FISH)方法检测乳腺癌HER-2/neu基因表达的临床意义。方法应用FISH法对2008年1月至2008年7月在首都医科大学附属北京天坛医院就诊的33例女性新发乳腺癌患者进行HER-2/neu基因检测,分析基因表达程度与临床病理特征之间的关系,比较基因和免疫组化(IHC)法蛋白表达的差别。结果33位受试者中HER-2/neu基因过表达率为39.4%,其过表达与肿瘤大小、绝经与否、临床分期之间差异无统计学意义(P>0.05)。该基因在有腋淋巴结转移组显著高于无淋巴结转移组(P<0.05),ER阴性组高于ER阳性组,差异有统计学意义(P<0.01)。PR阴性组与阳性组间差异无统计学意义。P53基因阳性组显著高于阴性组(P<0.05)。HER-2/neu基因过表达者11例为免疫组化HER-2蛋白强阳性病例;2例为中度阳性病例。结论FISH技术可稳定检测乳腺癌中HER-2/neu基因的表达程度,其过表达与绝经与否、肿瘤大小、临床分期无关,与腋淋巴结转移和P53基因表达成正相关,与ER呈密切负相关。HER-2蛋白高强度表达(3+)与基因扩增有极好的一致性,而中等强度表达(2+)必须进一步行FISH法基因检测。     

荧光原位杂交对乳腺癌HER2基因的检测及临床应用

目的探讨荧光原位杂交法(FISH)检测乳腺癌组织中人类表皮生长因子受体2(HER2)表达的临床意义。方法采用FISH和免疫组织化学(IHC)法分别检测28例乳腺癌标本中HER2基因扩增状况和HER2蛋白表达。结果在IHC法检测HER2蛋白表达(++)的22例标本中,FISH检出6例HER2基因扩增,16例无变化。在HER-2蛋白表达(+++)的6例标本中,FISH检出5例HER2基因扩增,1例无扩增。结论对于IHC法初筛为(++)的患者应再进行FISH检测,以确定HER-2基因的状态,从而确定是否应用曲妥珠单抗治疗。     

乳腺癌HER-2不同检测方法的比较研究

目的 比较荧光原位杂交技术（FISH）与免疫组织化学法（IHC）用于检测HER-2的效果。方法 将本院2020年1月-2022年3月期间收治的乳腺癌患者247例作为研究对象，均同时采用FISH与IHC检测HER-2基因或蛋白的表达情况，比较两种方法检测结果及一致性。结果 本研究纳入的247例患者均留取合适标本进行相关检查，结果表明HER-2蛋白表达采用免疫组化检测+++，可疑及+患者分别有8.10%(20例)，73.68%(182例)和10.12%(25例)，HER-2蛋白表达采用荧光原位杂交技术检测有扩增和无扩增患者分别为30.36%(75例)和69.64%(172例)。247例患者免疫组化检测HER-2结果为+++、++和+时与荧光原位杂交技术检测的符合率分别为85.00%、96.70%、20.00%，免疫组化检测HER-2结果为+++、++的202例患者中有97.03%的患者FISH检测有HER-2基因扩增，而结果为+的患者中有20.00%患者FISH检测有HER-2基因扩增。FISH和IHC检测结果经一致性检验后发现一致性较好（Kappa值=0.543,P <0.05）。...     

FISH及免疫组化技术检测乳腺癌Her-2基因与蛋白的临床应用价值

目的 分析免疫组化技术(IHC)检测石蜡标本乳腺癌组织中原癌基因-2(Her-2)蛋白表达与荧光原位杂交技术(FISH)检测Her-2基因扩增状态的临床应用价值.方法 IHC和FISH技术分别检测98例乳腺癌癌组织中的Her-2蛋白表达和Her-2基因扩增.结果 98例石蜡包埋乳腺癌组织中1例Her-2表达蛋白为阴性的患者中,Her-2 基因扩增亦为阴性,符合率100%(1/1);15例Her-2蛋白表达为(+)的患者中,Her-2 基因扩增为阴性的12例,符合率为 80.0%(12/15);49例Her-2蛋白表达为(++)的患者中,Her-2基因扩增为阳性的25例,符合率51%(25/49);33例Her-2蛋白表达为(+++)的患者中,Her-2 基因扩增为阳性的27例,符合率81.8%(17/21).IHC法初筛为阴性(-~+)和强阳性(+++)检测结果与FISH检测结果一致性较高(Kappa =0.602＞0.40,P＜0.01),且两法检测差异无统计学意义(χ2=0.508,P＞0.05).结论 IHC方法检测乳腺癌组织中Her-2蛋白表达阴性和强阳性与FISH检测结果一致性较高.     

110例乳腺癌患者HER-2基因扩增状况及其与临床病理特征的关系

目的在蛋白及基因水平检测乳腺癌中HER-2的表达,比较免疫组化（IHC）及荧光原位杂交（FISH）法检测结果,探讨其与乳腺癌患者的临床病理特征关系。方法应用免疫组化及荧光原位杂交法测定HER-2蛋白表达及基因扩增,并分析其与乳腺癌患者临床病理特征的相关性。结果与FISH的一致性在IHC检测HER-2（＋＋＋）和HER-2（＋/-）组较好,Kappa值=0.444,两者一致率为72.2%,而在HER-2（＋＋）组一致性较差。110例乳腺癌患者中,FISH检测有77例（70.0%）HER-2基因扩增。IHC法HER-2（＋＋＋）4例中全部有HER-2基因扩增;HER-2（＋＋）92例中有68例（73.9%）HER-2基因扩增;HER-2（＋/-）14例中有5例（35.7%）HER-2基因扩增。94例浸润性导管癌中66例（70.2%）有HER-2基因扩增,7例浸润性小叶癌中有4例（57.1%）HER-2基因扩增,9例其他肿瘤类型中有4例（44.4%）HER-2基因扩增。不同病理类型及浸润性导管癌的组织学分级间HER-2基因扩增阳性率差异无统计学意义（P〉0.05）。HER-2基因扩增与ER、PR阴性状态有相关性（P〈0.05）,与患者是否绝经无相关性（P〉0.05）。结论在HER-2（＋＋＋）和HER-2（＋/-）中常可以用IHC代替FISH检测HER-2基因扩增状况,而对于HER-2（＋＋）则应常规进行FISH检测。HER-2基因扩增状况与绝经、病理类型及浸润性导管癌组织学分级无相关性,与ER、PR表达呈负相关。HER-2基因可作为判断乳腺癌预后及拟订治疗方案的良好指标。     

乳腺癌中HER-2蛋白表达及基因扩增检测的比较研究

目的 比较免疫组化（IHC）法与荧光原位杂交（FISH）法检测乳腺癌组织HER-2状态,分析二者相关性.方法 应用IHC法与FISH法对56例女性新发乳腺癌行HER-2蛋白表达及基因扩增的检测.结果 56例受试者中HER-2蛋白表达（-）、（＋）、（＋＋）、（＋＋＋）者分别为9例（16.1%）、29例（51.8%）、11例（19.6%）、7例（12.5%）;有26例（46.4%）HER-2基因扩增,30例（53.6%）无扩增.HER-2基因扩增主要表现在HER-2（＋＋）和（＋＋＋）中,基因扩增率分别为72 7%和100%.HER-2（＋）中有11例（37.9%）出现基因扩增,HER-2（-）中未见基因扩增.两种方法检测结果的阳性率差异有统计学意义（χ2=19.778,P＜0.01）.HER-2（-）及HER-2（＋＋＋）与FISH结果一致性很好（Kappa=0.969）.HER-2（＋）及HER-2（＋＋）与FISH结果一致性较差（Kappa=0.271）.结论 IHC是HER-2表达初步的筛查方法,HER-2（-）和（＋＋＋）者与基因扩增情况有很好的一致性,可直接指导临床治疗.HER-2（＋）和（＋＋）者中有部分HER-2基因扩增阳性,如行靶向治疗需进一步行FISH检测.     

FISH检测平顶山地区乳腺癌组织中HER-2基因的表达

目的 FISH方法检测乳腺癌组织中人表皮生长因子2(Her-2)的扩增情况,并与免疫组化结果相比较,优化实验方法。方法用FISH方法及免疫组化检测乳腺癌Her-2的表达,分析相关性。结果 202例乳腺癌患者中,FISH检测Her-2基因扩增60例,阳性率29.7%(60/202),其中Her-2蛋白阴性,Her-2基因未扩增36例,扩增1例,符合率94.7%;Her-2蛋白(+),Her-2基因扩增12例,符合率18.5%;Her-2蛋白(++),Her-2基因扩增22例,符合率26.8%;Her-2蛋白(+++),Her-2基因扩增26例,符合率92.8%。结论 FISH检测准确率较高,IHC阴性和(+++)时与FISH结果一致性较好,可作为治疗依据,IHC(+)～(++)时仅能作初步筛查,明确Her-2情况仍需FISH检测。     

乳腺癌HER-2的表达与临床病理特征的关系

目的 探讨荧光原位杂交(FISH)和免疫组织化学(IHC)检测乳腺癌组织中人表皮生长因子受体2(HER-2)基因扩增及蛋白表达的一致性和相关性,及其与乳腺癌患者的临床病理特征的关系.方法 采用FISH法检测128例乳腺癌患者HER-2基因扩增状态,与IHC结果进行一致性及相关性分析,并比较其与乳腺癌患者的临床病理特征的相关性.结果 128例乳腺癌标本中,IHC与FISH结果符合率为90.6%,存在一致性(Kappa=0.405,P=0.000).两种检查结果呈正相关(r=0.655,P=0.000).ER表达与HER-2基因扩增及其蛋白表达状态呈负相关(r=-0.300,P=0.001;r=-0.223,P=0.011),而ER/PR状态与HER-2基因扩增状态呈负相关(r=-0.213,P=0.016).肿瘤分级与HER-2蛋白表达呈负相关(r=-0.293,P=0.008),而与HER-2基因扩增状态无关(P＞0.05).结论 IHC(+++)与基因扩增有较好的一致性,而IHC(+～++)者有必要进一步行FISH法检测基因状态.ER、ER/PR状态及肿瘤分级与HER-2基因扩增和(或)蛋白表达存在相关性.

Abstract：

Objective To investigate the concordance and correlation between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) assessment for HER-2 status in breast cancer patients and analyze their relationship to clinical characteristics. Methods A total of 128 samples of breast cancer tissue were analyzed retrospectively. FISH was employed to detect the HER-2 gene amplification. And the FISH findings were compared with IHC test results by analyzing the concordance and correlation between two results. And their relationships to the clinical characteristics were analyzed. Results The overall coincidence rate of IHC and FISH was 90. 6% ( kappa = 0.405, P = 0. 000 ). And the discordance was mainly found in the IHC ( + + ) group. A positive correlation was found between the two results ( r =0. 655, P=0. 000). The ER (estrogen receptor) expression was negatively correlated with HER-2 gene amplification and the expression of Her-2 protein ( r = - 0. 300, P = 0. 001;r = - 0. 223, P = 0.011 ).There was a negative correlation between ER/PR status and HER-2 gene amplification (r = -0.213, P=0.016). The similar results were found in subgroup analysis. Tumor grade was negatively correlated with the expression of Her-2 protein ( r = - 0. 293, P = 0. 008 ), but not with HER-2 gene amplification ( P ＞0. 05). Conclusion IHC is a preferred method to detect the Her-2 status in breast cancer. The strong positive expression ( + + + ) of HER-2 protein tested by IHC is strongly consistent with HER-2 gene amplification by FISH. But HER-2 gene amplification should be further detected by FISH in patients with HER-2 positive expression ( + - + + ) in order to guide the clinical diagnosis and treatment. ER, ER/PR (progesterone receptor)status and tumor grade are correlated with HER-2 gene amplification and/or the expression of Her-2 protein. This study helps improve the accuracy of judging HER-2 gene amplification according to the clinical and pathological features such as ER status and the results of IHC.     

荧光原位杂交和免疫组织化学技术检测乳腺癌HER-2基因扩增和蛋白表达状态对照研究

目的 比较荧光原位杂交(FISH)与免疫组织化学技术(IHC)在检测乳腺癌患者HER-2基因扩增和表达状态方面的应用.方法 采用FISH技术对66例IHC检测结果为HER-2基因过度表达(3+/2+)和低表达或无表达(1+/-)的乳腺癌石蜡切片进行HER-2基因扩增状态检测.结果 用FISH技术检测42例IHC结果显示HER-2基因过度表达(3+/2+)的标本,31例显示HER-2基因扩增,11例无扩增.检测24例IHC检测显示HER-2基因低度表达或无表达(1+/-)的标本,均未显示HER-2基因扩增.两组之间比较,Kappa系数为0.672,P<0.001,显示两项检测技术具有良好的一致性.另外.用FISH技术检测到部分病例显示17号染色体多体性,并且该多体性在HER-2高表达(3+/2+)的病例发生率显著高于低表达或无表达(1+/-)的病例(x~2=4.688,P=0.03).结论 FISH和ICH两项技术具有良好的一致性.IHC可作为HER-2基因扩增和表达状态检测的筛查手段.FISH技术可以作为检测HER-2基因扩增和17号染色体多体性的确诊手段.

Abstract：

Objective To evaluate the application of the immunohistochemistry (IHC) and the fluorescence in situ hybridization (FISH) in detecting the amplification and the expression of HER-2 gene in the breast cancer patients. Methods Sixty-six cases of paraffin-embeded breast cancer samples with overexpression, low or no expression of HER-2 gene as detected by IHC were analyzed for HER-2 gene amplification using FISH. Results Among the 42 samples with HER-2 gene overexpression (3+/2+) detected by IHC, 31 showed positive HER-2 gene amplification and 11 showed negative HER-2 gene amplification in FISH. In the 24 samples with low or no HER-2 gene expression (1+/-) detected by IHC, no HER-2 gene amplification was detected by FISH. The results of the two testing methods showed a good consistency with the kappa coefficient of 0.672 (P<0.001). We also found that the 17 chromosome polysomy in 42% of the samples and the incidence of 17 polysomy was significantly higher in the HER-2 gene overexpression (3+/2+) group than in low or no HER-2 gene expression (1+/-) group (x~2=4.688, P=0.03). Conclusion IHC can be used as a screening method for detecting HER-2 gene amplification, and FISH should be performed in cases of HER-2 gene overexpression (3+/2+) as detected by IHC.     

FISH与IHC用于乳腺癌HER-2检测的相关性分析

目的探讨荧光原位杂交法（FISH）和免疫组织化学法（IHC）两种方法检测HER-2与乳腺癌的相关性。方法收集50例手术切除的乳腺癌标本,FISH法检测细胞扩增情况,IHC法检测细胞膜上HER-2蛋白表达情况,对两种检测结果的一致性进行统计分析。结果FISH法与IHC法检测结果阳性的符合率为86．96％。结论FISH和ICH两项技术具有良好的一致性,且FISH对HER-2基因扩增更具敏感性,可作为确诊HER-2基因状态的方法。     

Comparison of fluorescence <Emphasis Type="Italic">in situ</Emphasis> hybridization and immunohistochemistry for assessment of HER-2 status in breast cancer patients

The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.