Immunohistochemistry for ERG Expression as a Surrogate for TMPRSS2-ERG Fusion Detection in Prostatic Adenocarcinomas
Immunohistochemistry for ERG Expression as a Surrogate for TMPRSS2-ERG Fusion Detection in Prostatic Adenocarcinomas
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DOI：
10.1097/pas.0b013e31821e8761
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发表时间：
2011-07-01
影响因子：
5.6
通讯作者：
Netto, George J.
中科院分区：
文献类型：
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作者：
Chaux, Alcides;Albadine, Roula;Netto, George J.
背景：在大约一半的前列腺癌(PCAS)中发现了TMPRSS2-ERG融合。荧光原位杂交(FISH)和逆转录聚合酶链式反应(RT-PCR)是这方面最常用的技术。本研究的目的是评估ERG免疫表达作为TMPRSS2-ERG融合在一大系列前列腺癌病例中的应用价值。材料和方法：427例耻骨后前列腺癌根治术组织标本构建10个组织芯片(TMA)。FISH分析以前是使用双色间期分离探针对ERG基因的50和30个区域进行的。使用商品化的兔抗ERG单抗(克隆EPR3864；表观组学，伯林格姆，CA)评价ERG的表达。结果：FISH检测到195例(45.7%)TMPRSS2-ERG融合。192例(45.0%)PCa组织表达ERG，而非肿瘤组织中无一例表达ERG。在含有FISH检测的TMPRSS2-ERG融合的肿瘤中，ERGH-评分显著高于FISH(P<；0.00001)，并且ERG免疫组织化学表达与FISH定义的TMPRSS2-ERG状态有很强的相关性(P<；0.00001)，其敏感性为86%(95%CI，80%-90%)，特异性为89%(95%CI，84%-93%)。受试者-操作特征曲线分析显示，ERG免疫表达对FISH检测TMPRSS2-ERG融合具有较高的准确性，曲线下面积为0.87(95%CI，0.84%-0.91；P<；0.00001)。结论：ERG免疫组织化学表达对判断TMPRSS2-ERG融合状态具有较高的准确性。ERG免疫组织化学可提供一种比FISH更准确、更简单、成本更低的方法来评估PCa中的ERG融合状态。
Background: TMPRSS2-ERG fusions have been identified in about one-half of all prostatic adenocarcinomas (PCas). Fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction have been the most commonly used techniques in this setting. The aim of this study was to evaluate the utility of ERG immunoexpression as a surrogate for TMPRSS2-ERG fusion in a large series of PCa cases.Materials and Methods: Four hundred twenty-seven radical retropubic prostatectomy tissue samples were used to construct 10 tissue microarrays (TMAs). FISH analysis was previously conducted using dual-color interphase break-apart probes for the 50 and 30 regions of the ERG gene. ERG expression was evaluated using a commercial rabbit anti-ERG monoclonal antibody (clone EPR3864; Epitomics, Burlingame, CA). Each TMA spot was independently assessed, and any nuclear staining positivity was considered as indicative of ERG expression.Results: TMPRSS2-ERG fusions were detected by FISH in 195 (45.7%) of the PCa cases. ERG immunoexpression was found in 192 (45.0%) of the PCa cases and in none of the nontumoral tissue samples. Mean ERG H-scores were significantly higher in tumors harboring FISH-detected TMPRSS2-ERG fusions (P < 0.00001), and there was a strong association between ERG immunohistochemical expression and the TMPRSS2-ERG status defined by FISH (P < 0.00001), with a sensitivity of 86% (95% CI, 80%-90%) and a specificity of 89% (95% CI, 84%-93%). Receiver-operating characteristic curve analysis showed that ERG immunoexpression had a high accuracy for identifying TMPRSS2-ERG fusions detected by FISH, with an area under the curve of 0.87 (95% CI, 0.84%-0.91; P < 0.00001).Conclusions: We found that ERG immunohistochemical expression has a high accuracy for defining the TMPRSS-ERG fusion status. ERG immunohistochemistry may offer an accurate, simpler, and less costly alternative for evaluation of ERG fusion status in PCa than FISH.