Abstract 2676: Single cell spatial profiling reveals ERBB2 and EGFR co-expression in primary esophageal adenocarcinoma and brain metastasis tumors

Abstract Esophageal adenocarcinoma is a prevalent and serious disease, ranking eighth globally, with a low survival rate of 15-25% and a rising incidence in the United States. However, the occurrence of brain metastasis in esophageal adenocarcinoma (EAC) is rare, affecting only approximately 2-6%. Despite its rarity, brain metastasis in EAC is associated with a poor prognosis, compounded by the limited availability of effective treatment options. Due to the infrequent occurrence of brain metastasis in EAC patients, our understanding of the tumor composition in these cases and how they differ from those in primary sites remains limited. To address these gaps, we analyzed the tumor microenvironment of brain metastasis tumors and their matched primary tumors using spatial transcriptomic data generated by the 10x Xenium Analyzer. By employing a brain tumor panel, an immune panel, and a custom panel, we characterized the tumor microenvironment, including neuronal and immune cell populations present in these samples. Overall, primary samples contained a higher proportion of immune cells such as macrophages, T cells, B cells, dendritic cells, plasma cells, and mast cells, compared to brain metastases, which had a greater composition of neuronal cells. We additionally investigated the oncogenic expression patterns at the single-cell level within these matched samples, revealing areas with high ERBB2 and EGFR expression density within malignant cell populations. Notably, brain metastasis samples contained a higher proportion of malignant cells co-expressing ERBB2 and EGFR than primary samples, suggesting clonal evolution during disease progression from primary to metastatic sites. Our findings indicate that ERBB2 and EGFR amplifications may represent potential targets for therapeutic interventions in these patients. These findings enhance our understanding of brain metastasis in EAC, offering insights into the tumor microenvironment that may guide future therapeutic strategies and improve clinical management for this previously understudied metastatic type. Citation Format: Nora Lawson, Lingqun Ye, Chae Yun Cho, Bo Zhao, Thomas Mitchell, Ines Martín, Andy Futreal, Kadir Akdemir. Single cell spatial profiling reveals ERBB2 and EGFR co-expression in primary esophageal adenocarcinoma and brain metastasis tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2676.