Background:Intraductal papillary mucinous neoplasms (IPMN) are now being identified with increasing frequency. IPMN of the main pancreatic duct (MD-IPMN) carries a significant risk of malignancy and surgery is usually recommended. Side branch IPMN (BD-IPMN) has a much lower risk of malignancy and can often be observed. However, BD-IPMN with the presence of symptoms, mural nodules, positive cytology or a cyst size larger than 3 cm is considered to have a high risk of malignancy and surgery is usually recommended.Carcinomas arising in IPMN are either the clinically more benign colloid carcinoma or the aggressive ductal adenocarcinoma. The diagnosis of carcinoma arising in IPMN using cytology or non-invasive imaging is challenging, often resulting in pre-emptive resection of benign lesions.Improved detection of malignancy using novel biomarkers may therefore improve diagnostic accuracy. One such novel promising biomarker is Plectin-1 (Plec-1). Plec-1 was identified in a phage display screen looking for unique markers of PDAC. We validated its use by immunohistochemistry (IHC) and in vivo imaging and found that Plec-1 directed imaging markers identify PDAC and distinguish it from benign pancreatic changes.The aim of this study was to determine whether Plec-1 can also be used to differentiate carcinoma arising in IPMN from benign IPMN.Methods:To assess the utility of Plec-1 as a biomarker in human IPMN, we assayed Plec-1 expression in normal pancreas (n=4), PDAC (n=19), benign (n=15) IPMN as well as carcinoma arising in IPMN (n=11) using IHC. Nerves, which were present in all slides and strongly stain for Plec-1, were used as a reference and to compare staining across slides.We evaluated benign IPMNs of all three epithelial phenotypes: gastric type (n=9), intestinal type (n=4) and oncocytic type (n=2). 11 carcinomas arising in IPMN were tested for Plec-1 expression: 6 colloid carcinomas and 5 ductal adenocarcinomas.Results:Plec-1 was not detected in normal pancreatic tissue (n=4) but was strongly expressed in all of the PDAC (n=19). Regardless of their epithelial type, none of the 15 benign IPMNs did stain for Plec-1. However, 5 of 5 ductal adenocarcinomas arising in IMPN stained for Plec-1. Interestingly, only 1 of 6 colloid carcinomas expressed Plec-1.Conclusion:The presence of Plec-1 in IPMN accurately identifies carcinoma arising in IMPN and is a good biomarker for the more aggressive ductal adenocarcinoma. However, the absence of Plec-1 can not be used to exclude cancer as colloid carcinomas rarely stain.