Abstract 6190: Patterns of EGFR and HER3 co-expression in solid tumors

Abstract

EGFR and HER3 are members of the ERBB receptor family and transmit growth and survival signals to cancer cells upon ligand binding. While both receptors are well established targets for cancer therapy, greater understanding of the relationship of their expression patterns in human cancer is needed to establish the scope of therapeutic potential. To evaluate the co-expression pattern of EGFR and HER3, cancer FFPE tissue microarrays from several cancer types were evaluated by immunofluorescence imaging and digital pathology, including cell-by-cell marker intensity and spatial analyses within the tumor and stromal compartments. Tissue cores were assigned H-scores, and individual cells were binned into 0, 1+, 2+, 3+ scoring based on established digital pathology methods using QuPath software. Spatial cytometry was used to further evaluate single-cell expression intensity. Analysis was conducted widely on multiple normal human tissues as well as cases of NSCLC adenocarcinoma n=86, NSCLC squamous cell carcinoma n=84, SCLC n=43, TNBC n=45, Biliary tract cancers n=80, Nasopharyngeal carcinomas n=60. Overall, the results of this analysis show the intermediate to high prevalence of EGFR and HER3 co-expression within each indication, as well as the frequency of EGFR and HER3 expressing cells. Furthermore, EGFR and HER3 heterodimers were confirmed by proximity ligation assay in certain index cases. Notably, of several observations, we observe NSCLC cases show a profound absence of EGFR- HER3+ tumor cells. Additionally, we observe that co-expression of EGFR and HER3 in normal human tissues is rare and of low signal intensity.
Citation Format: Matthew Wood, Cody Morrison, Jahan Salar Khalili, Yi Zhu. Patterns of EGFR and HER3 co-expression in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6190.