Abstract BACKGROUND Brain metastases from the gastrointestinal tract are a rare event (less than 10% of all brain lesions), but their impact on prognosis is remarkable. Their incidence is increasing due to earlier diagnosis and prolonged survival because of more effective treatment modalities. Because of the lack of evidence-based recommendations, no optimal treatment strategy has been defined. Hope might come from the discovery of new prognostic and predictive factors and their biological inhibitors. The aim of this study was to create a repository of matched primary cancer and brain metastases samples for clinicopathologic and molecular correlations of gastrointestinal tumors and to analyze changes in expression signatures between both samples. The main goal was to study the metastatic process and characterize the immune response by characterizing features such as invasiveness, vascular co-option, proliferation, stemness and cell-type heterogeneity between the matched tissues. METHODS We searched for patients at Stanford hospital with matched brain metastases from gastrointestinal tumors from 2008 to 2020 using the STARR database (The STAnford Research Repository, or STARR, is Stanford Medicine's approved resource for working with clinical data for research purposes.). Matched specimens mean that both brain metastases and gastrointestinal tumors were studied at Stanford University. FFPE blocks from these matched patients were sectioned and sections analyzed for gene expression analysis using nanoString nCounter technology and the immune-oncology panel. RESULTS Expression data from 32 matched patients with primary tumor and brain metastases will be discussed at the meeting. CONCLUSION We believe that analysis of changes in expression signatures between the matched primary gastrointestinal cancer and brain metastases will provide novel insights into the role for tumor factors, such as invasiveness, proliferation and stemness, and the tumor microenvironment in progression.