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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0204v1 16/2/613    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fendrich, V. Articles by Rothmund, M. Search for Related Content PubMed PubMed Citation Articles by Fendrich, V. Articles by Rothmund, M.

V Fendrich, Department of Surgery, University of Marburg, Marburg, Germany
R Ramerth, Department of Surgery, University of Marburg, Marburg, Germany
J Waldmann, Department of Surgery, University of Marburg, Marburg, Germany
K Maschuw, Department of Surgery, University of Marburg, Marburg, Germany
P Langer, Department of Surgery, University of Marburg, Marburg, Germany
D Bartsch, Department of Surgery, University of Marburg, Marburg, Germany
E Slater, Department of Surgery, University of Marburg, Marburg, Germany
A Ramaswamy, Pathology, University of Marburg, Marburg, Germany
M Rothmund, Department of Surgery, University of Marburg, Marburg, Germany

Correspondence: Volker Fendrich, Email: fendrich{at}med.uni-marburg.de

Abstract

Some 80 to 90 per cent of gastrinomas are located in the gastrinoma triangle. The natural history of the tumors depends on their origin. Duodenal gastrinomas are less aggressive than pancreatic primaries and infrequently develop liver metastases. The reason therefore is unclear. The transcription factor Pancreatic-duodenal homeobox 1 (Pdx1) is important in differentiation and development of the pancreas and duodenum. In development, Sonic hedgehog (Shh) expression establishes a sharp molecular boundary, which allows for the patterning of the duodenal and pancreatic epithelium. Pancreatic polypeptide (PP) is expressed in pancreatic islets and is known to be expressed in pancreatic endocrine tumors. This study aims to clarify the expression pattern of Pdx1, Shh and PP in gastrinomas. Tissue from 15 patients with duodenal and from 11 patients with pancreatic gastrinomas were evaluated for Pdx1 expression by immunohistochemistry (IHC). Furthermore, tissue from lymph node metastases from a undetected primary gastrinoma was analyzed. IHC revealed Pdx1 expression in pancreatic gastrinomas, but not in duodenal gastrinomas. In contrast, there was no Shh expression detectable in pancreatic gastrinomas, but in all duodenal gastrinomas. Shh expression combined with absence of Pdx1 expression in lymph node metastases from patients with an unknown location of the primary suggests a duodenal gastrinoma. We show for the first time that only pancreatic express Pdx1. Moreover, only duodenal gastrinomas express Shh, suggesting a different genetic background of these two tumors. The expression pattern of Pdx1, Shh and PP in resected metastases can help to locate an otherwise undetected primary gastrinoma.