下一代测序预测人表皮生长因子2在实体肿瘤中的过表达的保真度

IF 5.3 2区 医学 Q1 ONCOLOGY
Mya Tran, Christopher A Fausel, Steven Bray, Guanglong Jiang, Erica Cantor, Santosh Philips, Fei Shen, Bryan P Schneider
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引用次数: 0

摘要

目的:人表皮生长因子2 (HER2/ERBB2)最近在trastuzumab deruxtecan获批用于HER2过表达(3+)实体瘤后成为泛肿瘤不确定的靶点。HER2阳性目前通过免疫组织化学(IHC)和/或原位杂交(ISH)进行HER2扩增来评估,因为在许多情况下HER2过表达是继发于HER2基因扩增的。除乳腺癌/胃食管癌外,评估实体肿瘤过表达的最佳IHC评分方法仍不明确。下一代测序(NGS)在实践中经常使用,可以用来预测HER2阳性。然而,人们对这些方法之间的相关性知之甚少。我们试图评估NGS预测HER2过表达的能力。方法:我们比较了HER2 IHC和/或ISH结果与NGS检测的HER2扩增状态的一致性,这些患者在2021年9月至2024年10月期间转诊到印第安纳大学精密基因组学项目。结果:免疫组化检测出her2.3 +的病例占4.3%(1009例中43例)。当包括HER2 +/ISH阳性(ISH+)时,HER2阳性的总发生率为5.1%(51 / 1009)。20.9%(43 / 9)的HER2 +和75.0%(8 / 6)的HER2 +/ISH+患者的NGS未检测到HER2扩增。不同类型的NGS检测平台和样品状态的不一致性率不同,液体NGS的不一致性发生率最高(80.3%),使用相同样品进行检测时的不一致性发生率最低(26.7%)。结论:单纯依靠基于ngs的HER2扩增可能导致HER2阳性病例缺失,从而剥夺了患者抗HER2治疗的选择。NGS、IHC和/或ISH应作为最佳检测HER2阳性的补充工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fidelity of Next-Generation Sequencing to Predict Human Epidermal Growth Factor 2 Overexpression Across Solid Tumors.

Purpose: Human epidermal growth factor 2 (HER2/ERBB2) has recently become a pan-tumor-agnostic target after the approval of trastuzumab deruxtecan for solid tumors with HER2 overexpression (3+). HER2 positivity is currently assessed by immunohistochemistry (IHC) and/or HER2 amplification through in situ hybridization (ISH), owing to the fact that HER2 overexpression is secondary to HER2 gene amplification in many cases. Outside of breast/gastroesophageal cancer, the optimal IHC scoring method to assess overexpression across solid tumors remains undefined. Next-generation sequencing (NGS) is frequently used in practice and could be leveraged to predict HER2 positivity. However, less is known regarding the correlation between these methodologies. We sought to evaluate the ability of NGS to predict HER2 overexpression.

Methods: We compared the concordance of HER2 IHC and/or ISH results with HER2 amplification status detected by NGS in 1,009 patients with solid tumors who were referred to the Indiana University Precision Genomics program between September 2021 and October 2024.

Results: HER2 3+ by IHC was identified in 4.3% (43 of 1,009) of cases. When including HER2 2+/ISH-positive (ISH+), the overall incidence of HER2 positivity was 5.1% (51 of 1,009). HER2 amplification was not detected by NGS in 20.9% (9 of 43) of HER2 3+ and 75.0% (6 of 8) of HER2 2+/ISH+ cases. The rate of discordance varies across the type of NGS testing platform and sample status, with the highest incidence seen in liquid NGS (80.3%) and the lowest incidence observed when the same sample was used for testing (26.7%).

Conclusion: Relying solely on NGS-based HER2 amplification could result in missing cases of HER2 positivity and thus deprive patients of anti-HER2 therapy options. NGS, IHC, and/or ISH should be used as complementary tools for optimal detection of HER2 positivity.

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CiteScore
9.10
自引率
4.30%
发文量
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