Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome

J Clin Endocrinol Metab. 2007 Sep;92(9):3378-82. doi: 10.1210/jc.2007-0283. Epub 2007 Jul 3.


Context: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families.

Objective: In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach.

Design and patient: Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene.

Results: Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation.

Conclusion: Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics
  • Carcinoma, Signet Ring Cell / complications*
  • Carcinoma, Signet Ring Cell / diagnostic imaging
  • Carcinoma, Signet Ring Cell / genetics
  • Carcinoma, Signet Ring Cell / pathology
  • Gastrins / blood*
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Multiple Endocrine Neoplasia Type 1 / complications*
  • Multiple Endocrine Neoplasia Type 1 / diagnostic imaging
  • Multiple Endocrine Neoplasia Type 1 / pathology
  • Stomach Neoplasms / complications*
  • Stomach Neoplasms / diagnostic imaging
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Ultrasonography
  • Zollinger-Ellison Syndrome / complications*
  • Zollinger-Ellison Syndrome / diagnostic imaging
  • Zollinger-Ellison Syndrome / genetics
  • Zollinger-Ellison Syndrome / pathology


  • Cadherins
  • Gastrins