title: Non-islet origin of pancreatic islet cell tumors.
abstract: The histogenesis of pancreatic islet cell tumors was investigated by morphological identification of putative precursor lesions in pancreatic tissue from patients with multiple endocrine neoplasia type 1 (MEN1), tissue microdissection, and genetic analysis. MEN1 mutation and absence of the MEN1 wild-type allele in different precursor lesions strongly suggest that pancreatic islet cell tumors are derived from the ductal/acinar system but not from pancreatic islet tissue. Pluripotent cells within the exocrine pancreas appear capable of formation into small atypical accumulations of MEN1-deficient cells with both exocrine and endocrine phenotype. The findings suggest presence of multiple developmental aberrations in MEN1 pancreas that potentially serve as precursor material for neuroendocrine tumors.
authors.affiliation: Molecular Pathogenesis Laboratory, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. vortmeyera@ninds.nih.gov
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Vortmeyer
authors.forename: Steve
authors.initials: S
authors.lastname: Huang
authors.forename: Irina
authors.initials: I
authors.lastname: Lubensky
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D007516:Adenoma, Islet Cell / Q000209:etiology* / Q000473:pathology; D000483:Alleles; D002454:Cell Differentiation; D018095:Germ-Line Mutation; D006801:Humans; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications* / Q000235:genetics*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins