WCLC 2025 - Posters & ePosters-P2.06.44 More Than a Mutation: Prevalence of HER2 Overexpression, Amplification, and Mutations by Histology in NSCLC

P2.06.44 More Than a Mutation: Prevalence of HER2 Overexpression, Amplification, and Mutations by Histology in NSCLC

Pdf Summary

This study investigates the prevalence of HER2 alterations—including overexpression, amplification, and activating mutations—in non-small cell lung cancer (NSCLC), focusing on adenocarcinoma and squamous cell carcinoma (SCC) histologies. Given that HER2-directed therapies have shown efficacy primarily in HER2-mutated lung adenocarcinoma, the study aims to better characterize the frequency and distribution of HER2 as a therapeutic target.<br /><br />In a retrospective analysis of 9,395 NSCLC samples, HER2 protein expression was assessed using immunohistochemistry (IHC) scored with ASCO/CAP breast cancer guidelines, HER2 amplification was determined by fluorescence in situ hybridization (FISH), and HER2 mutations identified by next-generation sequencing (NGS). Statistical analysis employed Fisher’s exact test.<br /><br />Results demonstrated that HER2 overexpression (IHC 3+) was significantly more common in adenocarcinoma (2.7%) than SCC (1.3%), with a higher prevalence of HER2 amplification by FISH in adenocarcinoma (8.5%) versus SCC (3.9%). Pathogenic HER2 mutations were also more frequent in adenocarcinoma (1.4%) compared to SCC (0.3%), with the majority of mutations in adenocarcinoma being exon 20 insertions. Diverse patterns of HER2 alterations were present within adenocarcinoma, including cases with overlapping markers of overexpression, amplification, and mutation.<br /><br />The findings underscore the heterogeneity of HER2 aberrations in NSCLC and highlight the critical need for comprehensive HER2 testing across modalities in adenocarcinoma to identify patients who may benefit from targeted HER2 therapies. The study advances understanding of HER2 as a multi-faceted molecular target beyond mutation alone, advocating for its inclusion in routine molecular profiling in NSCLC.

Asset Subtitle

Jennifer Marks

Meta Tag

Speaker Jennifer Marks

Topic Pathology and Biomarkers

Keywords

HER2 alterations

non-small cell lung cancer

adenocarcinoma

squamous cell carcinoma

HER2 overexpression

HER2 amplification

HER2 mutations

immunohistochemistry

fluorescence in situ hybridization

next-generation sequencing