Expression of von Hippel-Lindau Gene Product (pVHL) and S100P in Cystic Neoplasms of the Pancreas - with an Implication for Their Roles in Tumorigenesis

Our recent study demonstrated the inverse correlation of expression of S100P and von Hippel-Lindau gene product (pVHL) in pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDA). This study investigates whether there is a correlation of expression of these two markers in common cystic neoplasms of the pancreas. Immunohistochemical stains for S100P and pVHL were performed on 97 cystic neoplasms of the pancreas, including 23 mucinous cystic neoplasms (MCNs), 39 intraductal papillary mucinous neoplasms (IPMNs), 12 solid pseudopapillary tumors (SPTs), and 23 serous microcystic adenomas (SMAs). The results demonstrated a nuclear and cytoplasmic staining pattern of S100P in 91.3% of MCNs and 100% of IPMNs. In contrast, none of the SPTs or SMAs was positive for S100P. All IPMNs and SPTs, and all S100P-expressing MCNs were negative for pVHL, including 20 MCNs and 20 IPMNs with low-grade dysplasia. All cases of SMA were positive for pVHL. Our data suggest 1) the inverse correlation of expression of S100P and pVHL in MCN and IPMN is similar to that in PanIN and PDA, suggesting a role of these two proteins in early tumorigenesis; 2) the loss of pVHL expression in MCN and IPMN supports the recent recategorization of these neoplasms without any cytological atypia as low-grade dysplasia instead of adenoma; 3) the loss of expression of pVHL in SPT supports the concept of an uncertain malignant potential of this entity; and 4) the lack of expression of S100P and expression of pVHL in SMA supports the benign nature of this entity.