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Special Features: Matthias Schott, Cornelia Sagert, Holger S. Willenberg, Sven Schinner, Uwe Ramp, Andrea Varro, Andreas Raffel, Claus Eisenberger, Kai Zacharowski, Aurel Perren, and Werner A. Scherbaum 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; 92: 3378-3382 [Abstract] [Full text] [PDF]

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Gastrin and gastric cancer in man

Helge L. Waldum, Gunnar Qvigstad, Tom Chr. Martinsen, Reidar Fossmark   (5 December 2007)

Gastrin and gastric cancer in man 5 December 2007
Helge L. Waldum, Professor, Senior Consultant Norwegian University of Science and Technology, Gunnar Qvigstad, Tom Chr. Martinsen, Reidar Fossmark Send letter to journal: Re: Gastrin and gastric cancer in man helge.waldum{at}ntnu.no Helge L. Waldum, et al.	We read with great interest the paper by Schott and co-workers (1). In the paper they describe a patient with multiple endocrine neoplasia type 1 (MEN1) with a gastrinoma and multiple enterochromaffin-like (ECL) cell-derived tumors as well as a signet-ring cell carcinoma in the stomach. They speculate that progastrins may have reduced the expression of E-cadherin leading to an E-cadherin negative signet-ring cell carcinoma (1). The paper is important because it for the first time describe a gastric cancer due to hypergastrinemia in man. It is well known that hypergastrinemia whether secondary to hypoacidity or gastrinoma induces ECL cell derived tumors (2). However, although such tumors are accepted to be malignant in animals (2) and also may metastasize in man (3), gastrin has not been accepted to cause gastric cancer in man. Nevertheless, we have previously shown that an important proportion of the gastric carcinomas are derived from the ECL cell (2). Even more important, in relation to the paper by Schott and co-workers (1), we have previously shown that most gastric carcinomas in patients with hypergastrinemia are derived from the ECL cell (4), and that a proportion of signet-ring cell carcinomas are of neuroendocrine origin (5). By using for instance tyramide signal amplification (4) to increase the sensitivity of their immunohistochemistry, we suppose that the signet-ring cancer cells found in the patient described by Schott and co-workers (1) will be shown to be neuroendocrine (antibodies towards chromogranin and synaptophysine) and also ECL cell derived (antibodies towards VMAT 2 and histidine decarboxylase). The role of gastrin in gastric carcinogenesis has been reviewed many times (2). If gastrin really promotes gastric carcinogenesis, long-term use of efficient inhibitors of gastric acid secretion will be expected to induce gastric carcinomas also in man (2). References 1. Schott M, Sageret C, Willenberg HS, Schinner S, Ramp U, Varro A, Raffel A, Eisenberger C, Zacharowski K, Perron A, Scherbaum WA 2007. Carcinogenic hypergastrinemia: Signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison’s syndrome. J Clin Endocrinol Metab 92: 3378-3382 2. Waldum HL, Fossmark R, Bakke I, Martinsen TC, Qvigstad G 2004. Hypergastrinemia in animals and man: causes and consequences. Scand J Gastroenterol 39: 505-509 3. Qvigstad G, Falkmer S, Westre B, Waldum HL 1999. Clinical and histopathological tumour progression in ECL cell carcinoids (“ECLomas”). APMIS 107: 1085-1093 4. Qvigstad G, Qvigstad T, Westre B, Sandvik AK, Brenna E, Waldum HL 2002. Neuroendocrine differentiation in gastric adenocarcinomas associated with severe hypergastrinemia and/or pernicious anemia. APMIS 110: 132-139 5. Bakkelund K, Fossmark R, Nordrum I, Waldum HL 2006. Signet-ring cells in gastric carcinomas are derived from neuroendocrine cells. J Histochem Cytochem 54: 615-621