title: Effect of chronic hypergastrinemia on human enterochromaffin-like cells: insights from patients with sporadic gastrinomas.
abstract: OBJECTIVE
  The effect of chronic hypergastrinemia alone on gastric enterochromaffin-like (ECL) cells in humans is largely unknown because in the common chronic hypergastrinemic states (atrophic gastritis, chronic proton pump inhibitor use), it is not possible to separate the effect of hypergastrinemia and other factors, such as gastritis or atrophy. Studies of patients with sporadic Zollinger-Ellison syndrome (ZES) allow this separation.
  
  
  METHODS
  In 106 patients with ZES, gastric biopsies were taken, and the qualitative ECL cell pattern/grade and the alpha-subunit of human chorionic gonadotropin (alpha-hCG) expression were determined.
  
  
  RESULTS
  In patients with active disease, 99% had ECL hyperplasia and abnormal alpha-hCG staining. Fifty percent had advanced changes in both of these, with 7% having dysplasia and 0% having carcinoids. Advanced ECL cell and alpha-hCG changes were most affected by the level of hypergastrinemia. For ECL cell changes, even mild hypergastrinemia had an effect. Advanced ECL change was also affected by the duration of drug treatment, cure status, and presence of atrophic gastritis, but not by sex or previous vagotomy. The alpha-hCG expression independently predicted dysplasia.
  
  
  CONCLUSIONS
  In humans, chronic hypergastrinemia alone causes advanced ECL cell change and abnormal expression of mucosal alpha-hCG. No threshold for this effect was detected, as reported by some, and in contrast to animal studies, sex and vagal tone did not play a major role. The long-term risk of developing gastric carcinoids with chronic hypergastrinemia is low in patients with sporadic gastrinomas (at least 100 times less than in patients with multiple endocrine neoplasia type 1 with ZES) for at least 15-20 years.
authors.affiliation: Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, USA.
authors.forename: Paolo L
authors.initials: PL
authors.lastname: Peghini
authors.forename: Bruno
authors.initials: B
authors.lastname: Annibale
authors.forename: Cinzia
authors.initials: C
authors.lastname: Azzoni
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.forename: Vito D
authors.initials: VD
authors.lastname: Corleto
authors.forename: Fathia
authors.initials: F
authors.lastname: Gibril
authors.forename: David J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
authors.forename: Cesare
authors.initials: C
authors.lastname: Bordi
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002908:Chronic Disease; D004759:Enterochromaffin Cells / Q000473:pathology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015408:Gastrinoma / Q000209:etiology; D005755:Gastrins / Q000097:blood*; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000209:etiology; D011446:Prospective Studies; D015043:Zollinger-Ellison Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
chemical_list: D005755:Gastrins; D015292:Glycoprotein Hormones, alpha Subunit