Die klinische Bedeutung der Expression von Pancreatic-duodenal homeobox 1 (Pdx1) und Sonic Hedgehog (Shh) in Gastrinomen des Pankreas und des Duodenums
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Philipps-Universität Marburg
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Abstract
Gastrinomas are counted among the neuroendocrine tumors and are quite rare. This is surely one of the most reasons, why gastrinomas are still not sufficiently researched, although they are known since 1955. Their clinic is summarized as Zollinger-Ellison-Syndrome (ZES), which can occur sporadically and as part of a genetic disease, the MEN1 syndrome. Patients suffer not only from reflux, ulcers and diarrhea; they must also fear metastasis, which occur in 60%. Healing can only be achieved by complete resection of the tumors, which are to 50-70% in the duodenal wall and to 30-50% in the pancreas. Unfortunately, at diagnosis metastases often already exist, which are the most important prognostic factor. So far, it was not possible to conclude from the metastases to the localization of the primaries, what was the impetus for this work.
For this dissertation one of the largest databases of neuroendocrine tumors was used, which is collected in the Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg since 1987. Despite this relatively long observation periods to be included in the database until August 2008, only 35 patients with a gastrinoma has been included, and from only 28 patient it was possible to obtain enough tissue for study, of which 15 were duodenal gastrinomas, 11 pancreatic gastrinomas, and 2 patients had lymph node metastases of unknown primaries. This is a very small number of cases compared with other tumors such as pancreatic cancer, which underlines the rarity of gastrinomas once again.
The tissues of the patients were processed by immunohistochemistry and were stained with the transcription factor Pdx1 (Pancreatic and duodenal homeobox gene 1) and a ligand of the Hedgehog signaling pathway, Sonic Hedgehog (Shh). Pdx1 is a transcription factor, which plays a major role especially in the embryonic development of the pancreas and also in the adult pancreas, where it is detectable in the islet cells and is involved in the expression of insulin. The PDX1 gene is located on chromosome 13q12.1 of human. Shh is located on chromosome 7q36 and is, with Indian Hedgehog (Ihh) and Desert Hedgehog (Dhh), part of the Hedgehog signaling pathway, which is one of the best understood signaling pathways in humans. It plays an important role in cell differentiation and organogenesis and is brought into connection with the development of various tumors.
In this study it could be improved, that Pdx1 was detected in 100% of pancreatic gastrinomas and their metastases and was not found in any of duodenal gastrinomas. Shh, however, was found in 100% of all duodenal and not found in any of pancreatic gastrinomas. In both lymph node metastases of unknown primaries could be detected Shh. This leads to presumption that they must have been metastases of duodenal gastrinomas.
We hope that in future these findings could help to identify lymph node metastases of an unknown primary, which could help to decrease the invasiveness of the surgical treatment.
One problem of this dissertation is surely the low number of cases, but, due to the rarity of the tumor, it would be very difficult to collect much larger number of cases.
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Created: 2011Issued: 2011-08-08Updated: 2011-08-08
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
gastrinomaPyloruserhaltende partielle DuodenopankreatektomieNeuroendokrine TumorePankreaslinksresektion
DFG-subjects
MEN ZwölffingerdarmHedgehog GastrinomZollinger-Ellison-SyndromBauchspeicheldrseExpressionZwölffingerdarmgeschwürGastrin
DDC-Numbers
610
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Ramerth, Ricarda: Die klinische Bedeutung der Expression von Pancreatic-duodenal homeobox 1 (Pdx1) und Sonic Hedgehog (Shh) in Gastrinomen des Pankreas und des Duodenums. : Philipps-Universität Marburg 2011-08-08. DOI: https://doi.org/10.17192/z2011.0457.
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This item has been published with the following license: In Copyright