Abstract
Intraductal oncocytic papillary neoplasm (IOPN) is a rare intraductal tumor of the pancreatobiliary system. Currently, little is known about its distinct characteristics, unlike intraductal papillary mucinous neoplasms (IPMN) and intraductal papillary neoplasms of the bile duct (IPNB). The present study compared 22 IOPNs (18 pancreatic and 4 biliary) with those of 61 IPMNs/8 IPNBs. IOPNs were classified into pure and combined types, depending on the coexistence of IPMN/IPNB. Multiple gene expression analysis (nCounter system) was performed, and hierarchical clustering analysis separated IOPNs(n = 4) and IPMNs(n = 3)/ IPNBs(n = 3), and pathway score analysis supported the result. Volcano plot identified follistatin (FST) as the most upregulated mRNA in IOPN in comparison to the gastric subtype (log2 fold change of 5.34) and the intestinal subtype (that of 5.81) of IPMN/IPNB. The expression of FST in IOPN was also high in quantitative polymerase chain reaction and immunohistochemical analysis. We also found lower apoptotic activity in IOPN, particularly in pure type, compared to high-grade or invasive IPMN/IPNB using immunohistochemistry for cleaved caspase 3. But, combined type IOPN was more similar to IPMN/IPNB than pure IOPN. In conclusion, we proved that IOPN, particularly pure IOPN, is distinct from IPMN/IPNB in FST mRNA overexpression and exhibits lower apoptotic activity.
Highlights
Intraductal oncocytic papillary neoplasm (IOPN) is a rare intraductal tumor of the pancreatobiliary system
All IOPN cases were pathologically diagnosed as high grade or more; a statistically significant difference was found in the histological grade between IOPN and intraductal papillary mucinous neoplasms (IPMN)/intraductal papillary neoplasms of the bile duct (IPNB) samples
Hierarchical clustering analysis of the normalized data indicated a distinct cluster for 4 pancreatobiliary IOPN specimens, whereas IPMN and IPNB specimens comprised another cluster (Fig. 1a)
Summary
Intraductal oncocytic papillary neoplasm (IOPN) is a rare intraductal tumor of the pancreatobiliary system. IOPNs of the pancreas and the bile ducts are characteristically similar and have been considered as counterpart tumors[3,4,5,6,7,8]. Similar to intraductal papillary mucinous neoplasm (IPMN) and intraductal papillary neoplasm of the bile duct (IPNB), IOPNs in these sites are characterized by intraductal papillae with delicate fibrovascular cores and frequent mucin hypersecretion. This study aims to identify specific characteristics of IOPN by performing multiple gene expression analysis/digital gene expression quantification. Because FST’s role includes the inhibition of TGF-β pathway and recent in vitro studies have revealed that FST inhibits apoptotic activity[12,13,14,15,16], we further investigated TGF-β mRNA expression and apoptotic activity among IOPN and IPMN/IPNB cases
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