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 E-cadherin gene have been shown to be associated with occurrence of diffuse gastric carcinomas in affected families.

Objective: In this study we investigated the histopathological and molecular findings in the gastrointestinal (GI) wall of a patient with multiple endocrine neoplasia type 1 (MEN1) 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 GI tract of a patient with MEN1 were immunostained for VMAT-2 and E-cadherin. Non-amidated 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 germline 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% that of the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germline mutation.

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