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Evaluation of Next Generation Sequencing for Detecting HER2 Copy Number in Breast and Gastric Cancers.
Pathology & Oncology Research ( IF 2.8 ) Pub Date : 2020-07-03 , DOI: 10.1007/s12253-020-00844-w
Dongfeng Niu 1 , Lei Li 2 , Yang Yu 2 , Wanchun Zang 2 , Zhongwu Li 1 , Lixin Zhou 1 , Ling Jia 1 , Guanhua Rao 2 , Lianju Gao 2 , Gang Cheng 2 , Ke Ji 3 , Dongmei Lin 1
Affiliation  

Amplicon-based next generation sequencing (NGS) approaches have been preferentially adopted by the clinical laboratories on the basis of a short turnaround time (TAT) and small DNA input needs. However, little work has been done to assess the amplicon-based NGS methods for copy number variation (CNV) detection in comparison with current standard methods like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The correlation between NGS based CNV detection and the later standard methods has remained unexplored. We developed an amplicon-based panel to detect human epidermal receptor growth factor (HER2) amplification in formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 280 breast cancer and 50 gastric cancer patients. Assessment by IHC and FISH was conducted in parallel, and descriptive statistics were used to assess the concordance. The copy number detected by NGS was correlated with either the average HER2 copy number (signals/cell) (r = 0.844; p < 0.001) or the HER2/CEP17 ratio (r = 0.815; p < 0.001). We determined a cut-off value for NGS to categorize HER2 amplification status by using 151 HER2 non-amplified FFPE samples. In breast cancer patients, the cut-off value was 2.910, with 95.35%, 98.67% and 97.29% sensitivity, specificity and concordance, respectively. However, this cut-off value displayed low sensitivity in gastric cancer patients (64.71%), and the following macrodissection procedure was not effective for increasing sensitivity (57.14%). Evaluation of HER2 copy number with NGS in our study was comparable with IHC and FISH in breast cancer patients, but concordance in gastric cancer was only moderate. The greater discordance in gastric cancer may reflect the underlying biological mechanisms, and further study is warranted. NGS-based HER2 assessment may decrease the equivocal HER2 determinations in breast cancer patients assessed by FISH/IHC.



中文翻译:

用于检测乳腺癌和胃癌中HER2拷贝数的下一代测序的评估。

基于实验室的周转时间(TAT)和少量DNA输入需求,临床实验室已优先采用基于扩增子的下一代测序(NGS)方法。但是,与当前的标准方法(如免疫组织化学(IHC)和荧光原位杂交(FISH))相比,评估基于拷贝子的NGS方法进行拷贝数变异(CNV)检测的工作很少。基于NGS的CNV检测与较新的标准方法之间的相关性尚待探索。我们开发了一个基于扩增子的面板来检测人类表皮受体生长因子(HER2)来自280名乳腺癌和50名胃癌患者的福尔马林固定石蜡包埋(FFPE)肿瘤组织样品中的PCR扩增。由IHC和FISH进行的评估是并行进行的,并使用描述性统计数据来评估一致性。NGS检测到的拷贝数与平均HER2拷贝数(信号/细胞)(r = 0.844;p  <0.001)或HER2 / CEP17比率(r = 0.815;p  <0.001)相关。我们通过使用151 HER2确定了NGS的临界值以对HER2扩增状态进行分类非扩增FFPE样品。在乳腺癌患者中,该临界值是2.910,敏感性,特异性和一致性分别为95.35%,98.67%和97.29%。但是,该临界值在胃癌患者中显示出较低的敏感性(64.71%),并且以下宏观解剖方法对增加敏感性无效(57.14%)。在我们的研究中,用NGS评价HER2拷贝数与乳腺癌患者的IHC和FISH相当,但胃癌的一致性仅中等。胃癌更大的不一致性可能反映了其潜在的生物学机制,有待进一步研究。基于NGS的HER2评估可能会降低模棱两可的HER2 通过FISH / IHC对乳腺癌患者进行的测定。

更新日期:2020-07-03
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