title: Sonic hedgehog and pancreatic-duodenal homeobox 1 expression distinguish between duodenal and pancreatic gastrinomas.
abstract: Some 80-90% of gastrinomas are located in the gastrinoma triangle, which includes the duodenum, the pancreatic head, and the hepatoduodenal ligament. The natural history of the tumors depends on their origin. Duodenal gastrinomas are much 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 embryonic development, Sonic hedgehog (Shh) expression establishes a sharp molecular boundary, which allows for the proper 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 duodenal and pancreatic gastrinomas. Tissue from 15 patients with duodenal and from 11 patients with pancreatic gastrinomas that underwent surgery between 1987 and 2007 at our institution because of a gastrinoma were evaluated by immunohistochemistry (IHC). Furthermore, tissue from lymph node metastases from two patients with a so far undetected primary gastrinoma was analyzed. IHC revealed strong Pdx1 expression in pancreatic gastrinomas, but not in duodenal gastrinomas. By contrast, there was no Shh expression detectable in pancreatic gastrinomas, but found in all duodenal gastrinomas. This pattern was also true for associated metastases. Shh expression combined with absence of Pdx1 expression in lymph node metastases from patients with an unknown location of the primary suggests a so far undetected duodenal gastrinoma. We show for the first time that only pancreatic, but not duodenal gastrinomas express Pdx1. Moreover, only duodenal gastrinomas express Shh, suggesting a different genetic background of these two tumors. Whereas the expression of Pdx1 in pancreatic gastrinomas might suggest their endocrine origin from islets, duodenal gastrinomas develop from a Pdx1 negative cell cluster. The expression pattern of Pdx1, Shh, and PP in resected metastases can help to locate an otherwise undetected primary gastrinoma.
authors.affiliation: Department of Surgery, Philipps-University Marburg, Baldingerstrasse, D-35043 Marburg, Germany. fendrich@med.uni-marburg.de
authors.forename: Volker
authors.initials: V
authors.lastname: Fendrich
authors.forename: Ricarda
authors.initials: R
authors.lastname: Ramerth
authors.forename: Jens
authors.initials: J
authors.lastname: Waldmann
authors.forename: Katja
authors.initials: K
authors.lastname: Maschuw
authors.forename: Peter
authors.initials: P
authors.lastname: Langer
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
authors.forename: Emily P
authors.initials: EP
authors.lastname: Slater
authors.forename: Annette
authors.initials: A
authors.lastname: Ramaswamy
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothmund
mesh_terms: D000328:Adult; D000368:Aged; D004379:Duodenal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015408:Gastrinoma / Q000378:metabolism* / Q000556:secondary; D053823:Hedgehog Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D011379:Prognosis; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C509239:SHH protein, human; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D010191:Pancreatic Polypeptide