WCLC 2025 - Posters & ePosters-P1.17.22 Concordance of HER2 Protein Overexpression by IHC and ERBB2 Gene Amplification by NGS in Lung Cancer

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This study investigated the concordance between HER2 protein overexpression (HER2-OE), detected by immunohistochemistry (IHC), and ERBB2 gene amplification (ERBB2-amp), detected by next-generation sequencing (NGS), in lung cancer patient samples. Using the NeoGenomics database, 2,960 lung cancer tissue samples simultaneously tested by both methods were analyzed.<br /><br />Key findings indicate that 28.2% of samples met HER2-OE criteria (IHC 2 or 3), while 22.2% were ERBB2 amplified by NGS. The overall concordance between IHC and NGS was 69.4%, with 10% testing positive by both assays and 59.5% negative by both. However, a significant proportion of samples with HER2 overexpression as indicated by IHC were not identified as ERBB2 amplified by NGS: approximately two-thirds of IHC 2 and one-third of IHC 3 samples were ERBB2-amp negative. This suggests that relying solely on NGS testing for ERBB2 amplification misses many cases of HER2 protein overexpression.<br /><br />The study highlights that standard clinical practice in lung cancer mainly uses NGS testing, which focuses on ERBB2 mutations and amplifications but may inadequately detect HER2 protein overexpression, potentially leading to under-identification of patients who could benefit from HER2-targeted therapies such as Trastuzumab deruxtecan (T-DXd). The data support incorporating HER2 IHC testing into routine diagnostic workflows to complement NGS and optimize patient selection for targeted therapy.<br /><br />Limitations include the use of breast cancer scoring criteria for HER2 IHC, absence of lung cancer subtype data, potential sample selection biases, and inability to distinguish between clinical settings. Despite these, results underscore the need for a multimodal diagnostic approach in lung cancer.<br /><br />In summary, combining HER2 IHC with ERBB2 NGS testing enhances detection of clinically relevant HER2-positive lung cancers to guide precision therapy, preventing undertreatment of patients with HER2 overexpression missed by NGS alone.

Asset Subtitle

Samrat Yeramaneni

Meta Tag

Speaker Samrat Yeramaneni

Topic Global Health, Health Services, and Health Economics

Keywords

HER2 protein overexpression

ERBB2 gene amplification

immunohistochemistry (IHC)

next-generation sequencing (NGS)

lung cancer

NeoGenomics database

HER2-targeted therapies

Trastuzumab deruxtecan (T-DXd)

diagnostic concordance

precision oncology