ERBB2 FISH and Chromosome Microarray Testing of Gastroesophageal Adenocarcinomas at a Single Institution.

Alexander Yu, S. Luikart, Gengming Huang, Song Han, Jianping Zhao, L. Soong, Jianli Dong
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Abstract

Overexpression/amplification of erb-b2 receptor tyrosine kinase 2 (ERBB2) is a major prognostic factor in gastroesophageal cancers; it is currently the only biomarker established for the selection of targeted therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). Current standard procedure for determining ERBB2 status in such patients is immunohistochemistry (IHC), followed by in situ hybridization (ISH), when IHC result is equivocal. Insufficient knowledge regarding the utilities of chromosomal microarray (CMA) has hindered its use as an adjunct tool in ERBB2 analysis. Here, we performed CMA on 7 formalin-fixed paraffin-embedded (FFPE) GEA specimens previously tested by ERBB2 fluorescence in situ hybridization (FISH) and evaluated the concordance and performance of CMA. CMA identified 4 (57.1%) samples with amplification of ERBB2, compared to 3 (42.9%) by FISH. CMA also detected several additional DNA copy number variants in these samples, which may have prognostic and therapeutic indications. Further case studies and clinical trials may provide evidence for the utility of CMA-based genomic studies in the management of patients with suspected ERBB2-positive gastroesophageal adenocarcinoma.
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ERBB2 FISH和染色体微阵列在单个机构检测胃食管腺癌。
erb-b2受体酪氨酸激酶2 (ERBB2)的过表达/扩增是胃食管癌的主要预后因素;它是目前唯一一个为晚期胃食管腺癌(GEA)患者选择靶向治疗而建立的生物标志物。目前确定此类患者ERBB2状态的标准程序是免疫组织化学(IHC),然后是原位杂交(ISH),当IHC结果模棱两可时。关于染色体微阵列(CMA)的实用性的知识不足阻碍了其作为ERBB2分析的辅助工具的使用。在这里,我们对先前用ERBB2荧光原位杂交(FISH)检测过的7个福尔马林固定石蜡包埋(FFPE) GEA标本进行了CMA,并评估了CMA的一致性和性能。CMA鉴定出4份(57.1%)样品扩增出ERBB2,而FISH鉴定出3份(42.9%)。CMA还在这些样本中检测到一些额外的DNA拷贝数变异,这可能具有预后和治疗适应症。进一步的病例研究和临床试验可能为基于cma的基因组研究在治疗疑似erbb2阳性胃食管腺癌患者中的应用提供证据。
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