title: ECL-cell carcinoids and carcinoma in patients homozygous for an inactivating mutation in the gastric H(+) K(+) ATPase alpha subunit.
abstract: A family with a missense variant of the ATP4A gene encoding the alpha subunit of the gastric proton pump (H(+) K(+) ATPase) has recently been described. Homozygous siblings were hypergastrinemic (median gastrin 486 pM) and had gastric tumours diagnosed at a median age of 33 years. In the current histopathological study, we further characterized the tumours found in the gastric corpus. The tumours had the histological appearance of carcinoids (NET G1 or G2) and were immunoreactive for the general neuroendocrine markers chromogranin A (CgA) and synaptophysin as well as the ECL-cell markers vesicular monoamine transporter 2 (VMAT2) and histidine decarbozylase (HDC). One of the tumours consisted of a NET G2 component, but also had a component with glandular growth, which morphologically was classified as an intestinal type adenocarcinoma. Many glands of the adenocarcinoma contained a large proportion of cells positive for neuroendocrine markers, especially the small vesicle marker synaptophysin and the cytoplasmic enzyme HDC. In conclusion, patients homozygous for an inactivating ATP4A mutation develop gastric ECL-cell carcinoids in their 3rd or 4th decade. The adenocarcinoma may be classified as neuroendocrine with ECL-cell differentiation.
authors.affiliation: Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Reidar
authors.initials: R
authors.lastname: Fossmark
authors.affiliation: Human Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.|Network of Research on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Calvete
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Pathology, St. Olav's Hospital, Trondheim, Norway.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mjønes
authors.affiliation: Human Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.|Network of Research on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Benitez
authors.affiliation: Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D002276:Carcinoid Tumor / Q000473:pathology*; D053379:Chromogranin A / Q000032:analysis; D019861:Enterochromaffin-like Cells / Q000201:enzymology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000172:deficiency* / Q000235:genetics*; D006640:Histidine Decarboxylase / Q000032:analysis; D006651:Histocytochemistry; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D020125:Mutation, Missense; D013274:Stomach Neoplasms / Q000473:pathology*; D016708:Synaptophysin / Q000032:analysis; D050493:Vesicular Monoamine Transport Proteins / Q000032:analysis; D055815:Young Adult
chemical_list: D053379:Chromogranin A; C493452:SLC18A2 protein, human; C569014:SYP protein, human; D016708:Synaptophysin; D050493:Vesicular Monoamine Transport Proteins; C000591756:ATP4A protein, human; D017506:H(+)-K(+)-Exchanging ATPase; D006640:Histidine Decarboxylase
keywords: Gastric proton pump; carcinoids; gastrin; neuroendocrine tumour; proton pump inhibitors