CP-16. PROTEOMIC ANALYSIS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA REVEALS A COMPLEX NETWORK OF ECM REMODELING

Abstract

Abstract BACKGROUND Adamantinomatous craniopharyngiomas (ACPs) are the most challenging pituitary tumors in children. Despite their histological classification as benign, ACPs exhibit an aggressive clinical demeanor, posing challenges in management and conferring a suboptimal quality of life. The anatomical intricacies of ACPs often preclude complete surgical excision. The greatest morbidity of ACP is associated with damage to the hypothalamus - iatrogenically or through direct invasion, which may be dependent upon extracellular matrix (ECM) remodeling. We endeavored to describe the ECM components of ACPs and the protein milieu that may alter the ECM. METHODS High throughput imaging mass cytometry (IMC) alongside conventional histological staining methods. IMC offers unparalleled resolution in detecting ECM constituents, which may play pivotal roles in tumor pathophysiology and could represent novel therapeutic targets. We also employed SomaScan, an innovative, high-throughput, aptamer-based protein quantification platform. SomaScan utilizes Slow Off-Rate Modified Aptamers (SOMAmer Reagents) for the measurement of a broad spectrum of proteins within various biological fluids, including plasma and cyst fluid. RESULTS We identified prominent collagen tracts within ACP, which are further interspersed with areas of increased fibrosis surrounding wet keratin, suggestive of focal inflammatory response to cyst fluid. SomaScan identified elevated levels of proteins implicated in neutrophil degranulation. Neutrophil degranulation plays a significant role in ECM remodeling, a process critical to tumor progression and invasion. The association of neutrophils with ECM remodeling in ACPs suggests a potential mechanism through which these tumors might facilitate their own growth and invasion. The elevated protein markers of neutrophil degranulation may also serve as potential biomarkers or therapeutic targets, offering a novel approach to managing these tumors. CONCLUSIONS By integrating the data from IMC and SomaScan, our findings reveal a complex interplay between ACPs and the immune system, particularly highlighting the role of neutrophils in the tumor microenvironment.