Validating HER2 copy number variation assessment by NGS: A comparative analysis with immunohistochemistry and in situ hybridization.

IF 2 4区医学 Q3 ONCOLOGY

Tumori Pub Date : 2025-07-08 DOI:10.1177/03008916251345409

Daniele Lorenzini, Rebecca Salvatori, Chiara Costanza Volpi, Desirè Viola Trupia, Monica Niger, Federico Nichetti, Matteo Duca, Silvia Damian, Adele Busico, Alessia Bertolotti, Katia Todoerti, Luca Agnelli, Andrea Vingiani, Giancarlo Pruneri

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引用次数: 0

Abstract

Introduction: Anti-HER2 drugs are becoming an important therapeutic option for various solid tumors, increasing the need for HER2 status testing. Comprehensive genomic profiling (CGP) panels, including FoundationOne®CDx, are commonly used to assess ERBB2 (encoding for HER2) copy number alterations. We aimed to evaluate the analytical validity of FoundationOne®CDx assay, by comparing ERBB2 copy number data with traditional HER2 status by immunohistochemistry (IHC)/in situ hybridization (ISH) assays in a heterogeneous cohort of solid tumor samples.

Methods: We retrospectively reviewed the 531 cases evaluated by FoundationOne®CDx in our Institution, and HER2 status by IHC/ISH could be internally analyzed in 68 cases, including 31 (45.5%) gastroesophageal, 17 (25.0%) colorectal, four (5.8%) breast and two (2.9%) cholangiocarcinoma patients.Tumors with estimated ERBB2 copy number ⩾ 4 by FoundationOne®CDx, and tumors with strong and complete (3+) membranous staining by IHC and/or a HER2/CEP17 ratio ⩾2 by ISH were considered NGS positive and IHC/ISH positive, respectively.

Results: We identified 21 NGS positive cases (30.9%); IHC/ISH analysis confirming overexpression/amplification in 16 cases (sensitivity: 76.2%), while among the 47 NGS negative cases, 45 were confirmed by IHC/ISH results (specificity: 90%), with a positive predictive value of 76.2% and a negative predictive value of 95.7%.

Conclusions: FoundationOne®CDx provides an accurate evaluation of ERBB2 copy number status and may represent a cost-effective option in metastatic cancer patients for whom NGS testing is recommended.

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通过NGS验证HER2拷贝数变异评估：与免疫组织化学和原位杂交的比较分析。

抗HER2药物正成为各种实体瘤的重要治疗选择，这增加了对HER2状态检测的需求。综合基因组分析（CGP）面板，包括FoundationOne®CDx，通常用于评估ERBB2（编码HER2）拷贝数的改变。我们旨在通过免疫组化(IHC)/原位杂交（ISH）方法比较ERBB2拷贝数数据与传统的HER2状态，来评估FoundationOne®CDx检测的分析有效性。方法：回顾性分析我院531例FoundationOne®CDx检测的患者，通过IHC/ISH对68例患者的HER2状态进行内部分析，其中胃食管癌31例（45.5%），结直肠癌17例（25.0%），乳腺癌4例（5.8%），胆管癌2例（2.9%）。通过FoundationOne®CDx估计ERBB2拷贝数大于或等于4的肿瘤，以及通过IHC和/或HER2/CEP17比率大于或等于或等于2的肿瘤，分别被认为是NGS阳性和IHC/ISH阳性。结果：NGS阳性21例（30.9%）；IHC/ISH分析证实过表达/扩增16例（敏感性76.2%），47例NGS阴性患者中，IHC/ISH结果证实45例（特异性90%），阳性预测值为76.2%，阴性预测值为95.7%。结论：FoundationOne®CDx提供了ERBB2拷贝数状态的准确评估，可能代表了NGS检测推荐的转移性癌症患者的成本效益选择。

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来源期刊

Tumori 医学-肿瘤学

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Tumori Journal covers all aspects of cancer science and clinical practice with a strong focus on prevention, translational medicine and clinically relevant reports. We invite the publication of randomized trials and reports on large, consecutive patient series that investigate the real impact of new techniques, drugs and devices inday-to-day clinical practice.