Objective: The usefulness of 2 novel biomarkers in pancreatic surgical and cytological specimens that could reliably differentiate non-neoplastic pancreatic duct and benign gut epithelium from pancreatic ductal adenocarcinoma (PDA) was evaluated. Study Design: A total of 14 pancreatic resection specimens (RSs), 23 endoscopic ultrasound-guided fine needle aspirations (EUS-FNAs) of PDA and 8 benign pancreatic EUS-FNAs were selected. Twelve of 14 RSs had corresponding EUS-FNAs with cell blocks (CBs). Non-neoplastic pancreatic tissue, including chronic pancreatitis, was evaluated in all RSs. Immunohistochemical stains for S100P and X-linked inhibitor of apoptosis protein (XIAP) were performed on tissue and CB sections. Staining intensity (0 no staining; 1+ weak; 2+ moderate; 3+ strong) and proportion of positive cells (less than 10% negative; 1+ 10–25%; 2+ 26–75%; 3+ greater than 75%) were assessed. Positive staining was defined as ≧10% cells with at least 1+ intensity. Results: The sensitivity and specificity of S100P and XIAP immunoreactivity for a diagnosis of PDA in RSs were both 100%. In contrast, the sensitivity and specificity in EUS-FNA CBs of S100P were 78.2 and 87.5% and of XIAP 82.6 and 50.0%, respectively. The combined sensitivity of S100P and XIAP was 100% in 12 RSs and 83.3% in the corresponding EUS-FNA CBs. Conclusion: Two novel biomarkers have very high sensitivity and specificity in the diagnosis of PDA in RSs. S100P has slightly lower sensitivity and higher specificity of PDA than XIAP in EUS-FNA specimens. We recommend using both biomarkers as cytological diagnostic adjuncts, especially in difficult cases of well-differentiated PDA versus reactive ductal epithelium.

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