Non-islet origin of pancreatic islet cell tumors.
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.
Vortmeyer
Alexander O
AO
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
Huang
Steve
S
Lubensky
Irina
I
Zhuang
Zhengping
Z
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*
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins