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Insulin-like growth factor-II in endocrine pancreatic tumours: Immunohistochemical, biochemical and in situ hybridization findings

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In earlier studies a high-molecular-weight (HMW) insulin-like growth factor-II (IGF-II) peptide was identified in adult human pancreas and localized to the insulin-producing B-cells. This peptide has now been investigated in neoplastic insulin cells. Forty endocrine pancreatic tumours and 17 pancreatic adenocarcinomas of ductal type were included in the study. All cases were investigated with immunohistochemical techniques using antibodies to IGF-II, insulin, pro-insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and vasoactive intestinal peptide (VIP). Frozen tissue from nine tumours and two normal pancreatic glands was extracted, gel separated, and quantified using radioimmunoassay. The tumours were also investigated by in situ hybridization. IGF-II-immunoreactive cells were found in nearly all the 18 insulin-producing tumours (16/18), in a minority of the other endocrine tumours, but not in pancreatic adenocarcinomas. All extracts from the endocrine tumours showed varying amounts of IGF-II and had different molecular-weight forms. The immunohistochemical and radioimmunoassay findings are both based on immunological binding and were further confirmed by Northern blot and in situ hybridization. These results show that IGF-II is expressed in insulin-producing tumours as well as in pancreatic tumours producing other peptides, in contrast to normal pancreatic islets where IGF-II is found exclusively in insulin-producing cells.

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Keywords: Insulin-like growth factor II (IGF-II); endocrine pancreatic tumour; immunohistochemistry; in situ hybridization; insulinoma

Document Type: Original Article

Affiliations: 1: Tumour Pathology Unit at the Department of Oncology and Pathology, 2: Department of Surgery, 3: Department of Clinical Neuroscience, and 4: Department of Surgery, and 5: Institute of Laboratory Medicine, Norwegian University of Science and Technology, Trondheim, Norway 6: Department of Molecular Medicine, Karolinska Institute and Hospital, Stockholm, Sweden 7: Department of Genetics and Pathology, University Hospital, Uppsala, Sweden

Publication date: February 1, 2001

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