LAUSR

Background. There are currently no reliable markers associated with aggressive behavior in well‐differentiated and moderately differentiated pancreatic neuroendocrine tumors. We aimed to determine whether expression of ubiquitin carboxyl‐terminal hydrolase L1 in conjunction with Ki67 can identify metastatic potential of well‐differentiated and moderately differentiated pancreatic neuroendocrine tumors from fine‐needle aspiration samples obtained by endoscopic ultrasound. Methods. Retrospective review of 48 patients with well‐differentiated and moderately differentiated pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound fine‐needle aspiration at a single center identified 35 biopsy samples with adequate material for analysis. Ubiquitin carboxyl‐terminal esterase L1 immunocytochemistry of primary pancreatic neuroendocrine tumors was performed along with Ki67 staining and scored semiquantitatively. The combination of ubiquitin carboxyl‐terminal esterase L1 score ≤4 (weak) and Ki67 ≥3% (high) was considered a positive test for predicting tumors associated with metastases. Results. Weak ubiquitin carboxyl‐terminal hydrolase L1 staining had 80% sensitivity, 65% specificity, 63% positive predictive value, and 81% negative predictive value to identify primary tumors associated with metastatic disease. The combination of weak ubiquitin carboxyl‐terminal hydrolase L1 staining and high Ki67 staining increased the test specificity to 95%. On multivariable analysis, combined positive test of weak ubiquitin carboxyl‐terminal esterase L1 staining and high Ki67 staining was an independent predictor of metastatic disease (P = .047). Conclusion. Ubiquitin carboxyl‐terminal hydrolase L1 is a novel biomarker for identifying malignant potential of primary well‐differentiated and moderately differentiated pancreatic neuroendocrine tumors and in combination with Ki67 is an independent predictor of development of metastatic disease.