title: Immunohistochemical investigation of F344/N rat islet cell tumors from national toxicology program studies.
abstract: In this study, we have investigated the immunoexpression of peptide hormones and mediators associated with human islet cell tumors in a group of proliferative islet cell lesions in F344 rats including islet cell hyperplasias, adenomas, and carcinomas, as defined by conventional histopathologic criteria. All proliferative islets expressed synaptophysin, although decreased expression intensity was observed in hyperplasias and adenomas. Most of the proliferative lesions expressed insulin, which generally decreased as lesions progressed toward malignancy. The distribution of glucagon, somatostatin, and gastrin-expressing cells was altered in proliferative islet lesions but did not comprise a large proportion of cells. Islet cell tumors were associated with increased nuclear expression of cyclin-dependent kinase 4 as well as increased proliferating cell nuclear antigen and decreased β-catenin expression. c-Myelocytomatosis oncogene expression was variable. This is the first study to describe the immunophenotype of islet cell tumors in the F344 rat and to show that islet cell tumors in the F344 rat exhibit similarities in protein expression to the human counterpart.
authors.affiliation: Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Koivisto
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Flake
authors.forename: Holly
authors.initials: H
authors.lastname: Kolenda-Roberts
authors.forename: Tiwanda
authors.initials: T
authors.lastname: Masinde
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.forename: Robert C
authors.initials: RC
authors.lastname: Sills
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hoenerhoff
mesh_terms: D000236:Adenoma / Q000473:pathology; D007516:Adenoma, Islet Cell / Q000473:pathology*; D000818:Animals; D002277:Carcinoma / Q000473:pathology; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000473:pathology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013004:Somatostatin / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D013004:Somatostatin; D005934:Glucagon; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4