title: Histopathological and Immunohistochemical Characterization of Methyl Eugenol-induced Nonneoplastic and Neoplastic Neuroendocrine Cell Lesions in Glandular Stomach of Rats.
abstract: Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells.
authors.affiliation: Integrated Laboratory Systems Inc., Research Triangle Park, North Carolina, USA.
authors.forename: Kyathanahalli S
authors.initials: KS
authors.lastname: Janardhan
authors.affiliation: Cellular and Molecular Pathology Branch, Division of National Toxicology Program, Research Triangle Park, North Carolina, USA.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Rebolloso
authors.affiliation: Charles River Pathology Associates, Durham, North Carolina, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hurlburt
authors.affiliation: Charles River Pathology Associates, Durham, North Carolina, USA.
authors.forename: David
authors.initials: D
authors.lastname: Olson
authors.affiliation: Integrated Laboratory Systems Inc., Research Triangle Park, North Carolina, USA.
authors.forename: Otis
authors.initials: O
authors.lastname: Lyght
authors.affiliation: Cellular and Molecular Pathology Branch, Division of National Toxicology Program, Research Triangle Park, North Carolina, USA.
authors.forename: Natasha P
authors.initials: NP
authors.lastname: Clayton
authors.affiliation: EPL Inc., Research Triangle Park, North Carolina, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Gruebbel
authors.affiliation: WIL Research, Hillsborough, North Carolina, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Picut
authors.affiliation: EPL Inc., Research Triangle Park, North Carolina, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Shackelford
authors.affiliation: Cellular and Molecular Pathology Branch, Division of National Toxicology Program, Research Triangle Park, North Carolina, USA herbert1@niehs.nih.gov.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Herbert
mesh_terms: D000818:Animals; D005054:Eugenol / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D055099:Neuroendocrine Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*
chemical_list: C005223:methyleugenol; D005054:Eugenol
keywords: chromogranin A; gastric; immunohistochemistry; methyl eugenol; neuroendocrine; synaptophysin