title: Neuropilin-2 is a novel marker expressed in pancreatic islet cells and endocrine pancreatic tumours.
abstract: Neuropilin-2 (NP-2) is a cell surface transmembrane protein originally characterized as a receptor for the type 3 semaphorins, and more recently for a number of vascular endothelial growth factor (VEGF) isoforms. NP-2 expression has been recently localized to a subset of neuroendocrine cells in the gastrointestinal tract. The aim of this study was to define the expression pattern of NP-2 in normal pancreatic islets and to determine the utility of NP-2 expression as a diagnostic marker of pancreatic endocrine tumours. Paraffin-embedded tissue sections from 30 endocrine pancreatic tumours (EPTs) and from normal pancreas were immunostained with a rabbit polyclonal antibody generated towards NP-2. Nineteen of the tumours were hormonally functional (nine insulinomas, nine gastrinomas, and one glucagonoma). The NP-2 staining pattern was correlated with islet cell hormone expression. In addition, NP-2 expression was evaluated in other normal neuroendocrine tissues and neuroendocrine neoplasms. In normal pancreas, NP-2 stained a distinct subset of islet cells situated primarily at the islet periphery. Double immunohistochemical staining revealed co-localization with glucagon-expressing cells. Moderate to strong NP-2 staining was present in 27 of 30 EPTs. Serial staining of the pancreatic tumours with insulin, gastrin, glucagon, pancreatic polypeptide (PP) or somatostatin did not reveal a distinct pattern of co-localization. NP-2 expression was not detected in neuroendocrine cells outside the gastroenteropancreatic system, or in their corresponding neoplasms, except for focal staining in one bronchial carcinoid tumour. In conclusion, the vast majority of EPTs examined expressed NP-2, suggesting its utility as a diagnostic marker for these tumours. The function of NP-2 in islet cell biology or tumourigenesis remains to be elucidated.
authors.affiliation: Department of Pathology, Carmel Medical Center and Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Tzafra
authors.initials: T
authors.lastname: Cohen
authors.forename: Yael
authors.initials: Y
authors.lastname: Herzog
authors.forename: Asia
authors.initials: A
authors.lastname: Brodzky
authors.forename: Joel K
authors.initials: JK
authors.lastname: Greenson
authors.forename: Samuel
authors.initials: S
authors.lastname: Eldar
authors.forename: Zoya
authors.initials: Z
authors.lastname: Gluzman-Poltorak
authors.forename: Gera
authors.initials: G
authors.lastname: Neufeld
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
mesh_terms: D007516:Adenoma, Islet Cell / Q000175:diagnosis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003937:Diagnosis, Differential; D015408:Gastrinoma / Q000175:diagnosis / Q000378:metabolism; D005935:Glucagonoma / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007340:Insulinoma / Q000175:diagnosis / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000378:metabolism; D039942:Neuropilin-1; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D039942:Neuropilin-1