Multinational proficiency tests for EGFR exon 20 insertions reveal that the assay design matters

Ihle MA, Heydt C, Schultheis AM, Stöhr R, Haller F, Herold S, Aust D, Dietmaier W, Evert M, Eszlinger M, Haak A, Laßmann S, Vorholt D, Breitenbücher F, Werner M, Streubel A, Mairinger T, Grassow-Narlik M, Merkelbach-Bruse S (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 14

Article Number: 13069

DOI: 10.1038/s41598-024-63821-2

Abstract

Insertion mutations in exon 20 of the epidermal growth factor receptor gene (EGFR exon20ins) are rare, heterogeneous alterations observed in non-small cell lung cancer (NSCLC). With a few exceptions, they are associated with primary resistance to established EGFR tyrosine kinase inhibitors (TKIs). As patients carrying EGFR exon20ins may be eligible for treatment with novel therapeutics—the bispecific antibody amivantamab, the TKI mobocertinib, or potential future innovations—they need to be identified reliably in clinical practice for which quality-based routine genetic testing is crucial. Spearheaded by the German Quality Assurance Initiative Pathology two international proficiency tests were run, assessing the performance of 104 participating institutes detecting EGFR exon20ins in tissue and/or plasma samples. EGFR exon20ins were most reliably identified using next-generation sequencing (NGS). Interestingly, success rates of institutes using commercially available mutation-/allele-specific quantitative (q)PCR were below 30% for tissue samples and 0% for plasma samples. Most of these mutation-/allele-specific (q)PCR assays are not designed to detect the whole spectrum of EGFR exon20ins mutations leading to false negative results. These data suggest that NGS is a suitable method to detect EGFR exon20ins in various types of patient samples and is superior to the detection spectrum of commercially available assays.

Authors with CRIS profile

Robert Stöhr Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Florian Haller Professur für Diagnostische Molekularpathologie

Involved external institutions

Universitätsklinikum Köln DE Germany (DE) Universitätsklinikum Halle (Saale) DE Germany (DE) HELIOS Kliniken DE Germany (DE) Qualitätssicherungs-Initiative Pathologie QuIP GmbH (QuIP) DE Germany (DE) Universität Regensburg DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Janssen-Cilag GmbH DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE)

How to cite

APA:

Ihle, M.A., Heydt, C., Schultheis, A.M., Stöhr, R., Haller, F., Herold, S.,... Merkelbach-Bruse, S. (2024). Multinational proficiency tests for EGFR exon 20 insertions reveal that the assay design matters. Scientific Reports, 14. https://doi.org/10.1038/s41598-024-63821-2

MLA:

Ihle, Michaela A., et al. "Multinational proficiency tests for EGFR exon 20 insertions reveal that the assay design matters." Scientific Reports 14 (2024).

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