Inflammatory protein profiling of pancreatic cyst fluid using EUS-FNA in tandem with cytokine microarray differentiates between branch duct IPMN and inflammatory cysts

Background: Diagnosis of pancreatic cystic neoplasms remains problematic. We hypothesize that inflammatory mediator proteins in pancreatic cyst fluid can differentiate branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) and pancreatic inflammatory cysts. We aim to 1) detect inflammatory mediator proteins (IMPs) using a multiplexed IMP-targeted microarray in pancreatic cyst fluid obtained during endoscopic ultrasound fine needle aspiration (EUS-FNA) and 2) compare IMP profiles in pancreatic cyst fluid from BD-IPMNs and inflammatory cysts. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 inflammatory cysts) was obtained by EUS-FNA and analyzed directly with a multiplexed microarray assay to determine concentrations of 89 IMPs. Statistical analysis was performed using non-parametric methods. Results: Eighty-three of the 89 assayed IMPs were detected in at least one of the 10 patient samples. Seven IMPs were detected in BD-IPMN but not inflammatory cysts, while eleven IMPs were identified in inflammatory cysts but not BD-IPMN. Notably, granulocyte-macrophage colony-stimulating factor (GM-CSF) expression was present in all five inflammatory cyst samples. Hepatocyte growth factor (HGF) was present in significantly higher concentrations in inflammatory cysts compared to BD-IPMN. Conclusion: Our exploratory analysis reveals that GM-CSF and HGF in EUS-FNA-collected pancreatic cyst fluid can distinguish between BD-IPMN and inflammatory cyst. Coupling microarray molecular techniques to EUS-FNA may represent a major step forward to our understanding complex pancreatic disease.