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- Title
Carcinogenic Hypergastrinemia: Signet-Ring Cell Carcinoma in a Patient with Multiple Endocrine Neoplasia Type 1 with Zollinger-Ellison’s Syndrome.
- Authors
Schott, Matthias; Sagert, Cornelia; Willenberg, Holger S.; Schinner, Sven; Ramp, Uwe; Varro, Andrea; Raffel, Andreas; Eisenberger, Claus; Zacharowski, Kai; Perren, Aurel; Scherbaum, Werner A.
- Abstract
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
Journal of Clinical Endocrinology & Metabolism, 2007, Vol 92, Issue 9, p3378
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jc.2007-0283