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HER-2基因显色原位杂交与免疫组织化学检测对比研究

目的：对乳腺癌HER-2/neu/c-erbB-2（HER-2）显色原位杂交（chromogenicin situhybridization,CISH）检测和免疫组织化学（immunohistochemistry,IHC）表达两者之间进行对比研究。方法：选择乳腺癌的组织蜡块44例,经HER-2 IHC蛋白表达;阴性9例,（＋）9例,（艹）13例,（）13例。从中选取经HER-2 IHC表达阳性的乳腺癌22例[包括HER-2 IHC表达（＋）9例和HER-2 IHC表达（）13例]作回顾性CISH基因检测。结果：HER-2 IHC表达（＋）9例一组,经CISH基因检测9例均无基因扩增;HER-2 IHC表达（）13例一组,CISH无基因扩增2例（15.38%）,基因检测不理想1例（7.76%）,基因扩增10例,两种检测方法符合率76.92%,两者有高度一致性（P=0.001）。HER-2 IHC表达（）和CISH基因检测扩增与乳腺癌类型间有一定相关性（P〈0.05）。结论：CISH基因检测与IHC表达（）组,两者具有很高的一致性。IHC可作为乳腺癌HER-2筛选的首选方法,对于HER-2 IHC表达（ 卅）病例,经CISH基因检测,两者符合率高,CISH基因检测较IHC更准确,证实HER-2／neu扩增的患者可从采用抗HER-2单克隆抗体治疗中获益。     

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）。...     

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.     

FISH与IHC技术检测乳腺癌Her2状态的对比研究

目的比较荧光原位杂交法（FISH）与免疫组化法（IHC）检测乳腺癌组织中Her2基因扩增和蛋白表达的差异性和相关性。方法IHC法检测56例乳腺癌细胞膜上Her2蛋白表达情况,FISH法检测细胞核内Her2基因扩增情况,Х^2检验及kappa检验对两种方法检测结果进行统计分析。结果两种方法的检测Her2阳性率差异有统计学意义（Х^2=39．867,P〈0．05）;IHC法检测Her2蛋白0～1＋与3＋之间,通过FISH法检测Her2基因扩增的一致性好（k=0．906,P〈0．05）;而IHC检测Her2蛋白2＋与3＋之间,FISH检测Her2基因扩增一致性较差（k=0．357。P〈0．05）。结论IHC检测Her2蛋白为2＋的需做FISH检测,以明确Her2基因扩增的情况,FISH检测法提高了诊断的准确性和特异性。     

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。     

荧光原位杂交检测乳腺癌人表皮生长因子受体2基因扩增及与临床病理特征的关系

目的：探讨荧光原位杂交法(fluorescence in situ hybridization, FISH)及免疫组织化学法(immunohistoche mistry, IHC)检测乳腺癌人表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）的一致性,及HER-2基因扩增与乳腺癌临床病理特征的关系。方法：对北京大学第三医院病理科2008年1月至10月的乳腺浸润性导管癌病例中选取的41例进行HER-2基因扩增的FISH检测和蛋白表达的IHC检测,并对HER-2基因扩增与雌激素受体（estrogen receptor,ER）、组织学分级、癌周脉管内癌栓、腋窝淋巴结转移的关系进行统计学分析。结果：41例乳腺浸润性导管癌中,HER-2基因扩增患者15例,为IHC检测+++者8例,++者6例,+者1例,阴性者0例,分别占IHC+++、++、+及阴性者病例总数的88.89%（8/9）、42.68%（6/14）、8.33%（1/12）及0%（0/6）。HER-2基因扩增率在不同组织学分级的乳腺浸润性导管癌中差异无统计学意义（P=0.095）。HER-2基因扩增率在ER阴性及弱阳性（+）组高于ER强阳性（++或+++）组（P=0.018）,可见脉管内癌栓组高于未见脉管内癌栓组（P=0.000）,同侧腋窝淋巴结有转移组高于腋窝淋巴结无转移组（P=0.025）。结论：FISH技术可较稳定地应用于乳腺癌HER-2基因扩增的检测,IHC++的患者需进一步行FISH检测;HER-2基因扩增与ER表达呈负相关,与癌周脉管内癌栓、腋窝淋巴结转移呈正相关。     

改良荧光原位杂交技术检测乳腺癌HER2基因

目的探讨改良荧光原位杂交（fluorescent in situ hybridization,FISH）技术在检测乳腺癌HER2基因中的应用。方法对52例经免疫组化（immunohistochemistry,IHC）法检测HER2的乳腺癌标本行改良FISH法检测HER2基因扩增情况,Kappa检验法对两种检测结果的一致性进行统计分析。结果改良FISH法成功率高,与IHC法检测结果一致性好,两者实际一致率为88.5%（K=0.757,P=0.000）。结论改良FISH技术可作为最终确诊HER2基因状态的方法 。     

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.     

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.     

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。     

荧光原位杂交与免疫组化检测结直肠癌组织HER-2基因扩增或蛋白表达情况的研究

目的:用免疫组化(IHC)和荧光原位杂交技术(FISH)检测结直肠癌组织中HER-2蛋白表达或基因扩增状况,探讨HER-2在结直肠癌中的表达及临床意义.方法:采用IHC EnVision法检测68例结直肠癌及40例癌旁粘膜组织中HER-2蛋白的表达情况,并分析其与结直肠癌临床病理特征和预后的关系;对IHC(++)和(+...     

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.     

HER-2蛋白表达和基因扩增与乳腺癌预后的关系

目的 探讨HER-2蛋白表达和基因扩增与乳腺癌淋巴结转移和雌激素受体（ER）、孕激素受体（PR）的关系.方法 采用免疫组化SP法和荧光原位杂交法检测64例乳腺癌新鲜标本中的HER-2蛋白表达和基因扩增情况,并结合ER、PR及淋巴结转移情况对比分析.结果 64例中HER-2蛋白表达强阳性15例,阳性7例,弱阳性3例,阴性39例,其中基因过表达（免疫组化检测强阳性或阳性）率为37.5%;基因扩增20例.无扩增44例.扩增率31.3%.免疫组化与荧光原位杂交检测符合率为90.9%（P〈0.05）.ER、PR表达情况与HER-2蛋白表达和基因扩增呈负相关（r=-0.36、-0.35,P〈0.05）,ER和PR均阴性者HER-2蛋白表达率（60.0%）及基因扩增率（55.0%）明显高于ER和（或）PR阳性者（分别为22.7%、20.5%）.差异均有统计学意义（×2=8.47、7.64,均P〈0.05）.淋巴结转移情况与HER-2蛋白表达及基因扩增无关（r=0.16、0.22,P〉0.05）.结论 HER-2蛋白表达和基因扩增提示乳腺癌预后不良,HER-2及ER、PR在乳腺癌的治疗中有着重要作用,免疫组化可作为检测HER-2基因状态的首选方法 ,但对于HER-2＋＋者需进一步行荧光原位杂交检测.HER-2蛋白表达和基因扩增与淋巴结转移无关.     

FISH检测乳腺癌组织HER-2原癌基因50例分析

目的:探讨荧光免疫原位杂交法(FISH)检查乳腺癌HER-2基因扩增在临床中的应用价值。方法:选取50例乳腺癌手术患者,免疫组化染色方法检查乳腺癌组织中HER-2蛋白表达,FISH检查HER-2基因扩增情况,比较二者之间差异。结果:50例乳腺癌中免疫组化方法检测HER-2蛋白表达,者7例,者21例,+者17例;FISH检查50例中有8例出现HER-2基因扩增,42例无扩增。两种检测方法检测阳性结果有显著性差异(P<0.01)。结论:免疫组化检测可做为HER-2表达状态的初筛,对于初筛阳性患者有必要进行FISH检测,有助于指导临床应用赫赛汀(Herceptin)的治疗及对患者预后的判断。     

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。