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Ghrelin Immunoreactive Cells in Gastric Endocrine Tumors and Their Relation to Plasma Ghrelin Concentration: Ghrelin in Gastric Endocrine Tumors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Onkologisk endokrinologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Klinisk kemi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2008 (English)In: Journal of Clinical Gastroenterology, ISSN 0192-0790, E-ISSN 1539-2031, Vol. 42, no 4, 381-388 p.Article in journal (Refereed) Published
Abstract [en]

GOALS: Our aim was to elucidate the incidence and distribution pattern of ghrelin-immunoreactive (IR) cells in various types of human gastric endocrine tumors, and their surrounding mucosa, and relate the findings to total ghrelin concentrations in plasma. BACKGROUND: It has been demonstrated previously, that ghrelin-IR cells are present not only in normal human gastric oxyntic mucosa, but also in all types of enterochromaffinlike (ECL) cell carcinoids (ECL-CCs), and in mucosal regions affected by ECL cell hyperplasia. STUDY: Forty-eight gastric endocrine tumors were included in the study: 32 type I ECL-CCs, 3 type II, 9 type III, 1 non-ECL-CC, and 3 poorly differentiated endocrine carcinomas. The tumors were analyzed immunohistochemically with antibodies raised versus chromogranin A, synaptophysin, serotonin, somatostatin, vesicular monoamine transporter 2 and ghrelin. Total ghrelin in plasma was measured in 20 patients, using a commercial radioimmunoassay kit. RESULTS: Ghrelin-IR cells were found in all types I and II ECL-CCs but in only a few cases of the other tumors. Ghrelin-IR cells were also found among the hyperplastic endocrine cells in the mucosa surrounding types I and II, where they showed diffuse, linear, nodular and adenomatoid hyperplasia patterns. In type III ECL-CCs and poorly differentiated endocrine carcinomas, only diffuse and linear ghrelin-IR cell hyperplasia was present in the oxyntic mucosa in about half of the cases, whereas the mucosa of the non-ECL-CC did not show this feature. CONCLUSIONS: Despite the frequent occurrence of ghrelin-IR cells in both the neoplastic parenchyma and the oxyntic mucosa, plasma total ghrelin concentrations remained within the reference range and can therefore not be used as a clinical marker to identify ghrelin expressing ECL-CCs or ghrelin cell hyperplasia.

Place, publisher, year, edition, pages
2008. Vol. 42, no 4, 381-388 p.
Keyword [en]
ECL cells, gastric endocrine tumor, ghrelin, immunohistochemistry, radioimmunoassay
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97241DOI: 10.1097/MCG.0b013e318032338cISI: 000254629300011PubMedID: 18277901OAI: oai:DiVA.org:uu-97241DiVA: diva2:172092
Available from: 2008-05-06 Created: 2008-05-06 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Characterization of Endocrine Cells and Tumours in the Stomach
Open this publication in new window or tab >>Characterization of Endocrine Cells and Tumours in the Stomach
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Enterochromaffin-like (ECL) and ghrelin cells, in the human gastric mucosa and in gastric endocrine tumours (GETs), were subclassified with respect to immunohistochemical reaction vs. vesicular monoamine transporter 2 (VMAT-2), ghrelin/obestatin, and histidine decarboxylase (HDC). The immunohistochemical expression of ghrelin/obestatin and HDC in GETs was related/correlated to plasma ghrelin/obestatin and urinary methyl imidazole acetic acid (U-MeImAA) excretion respectively, with the intention of identifying markers for these tumour types.

ECL cells in the gastric mucosa appear either with VMAT-2 only, or with HDC immunoreactivity only, or they can express both proteins; but in GETs the transporter protein and the enzyme were almost always co-expressed in the same cells. Furthermore, ghrelin and obestatin were co-localized in the same cells in the gastric mucosa and in the tumours. In the gastric mucosa, occasional ghrelin/obestatin cells expressed VMAT-2, but in GETs these proteins were always co-localized. Ghrelin expressing cells were non-immunoreactive to HDC. Plasma ghrelin/obestatin concentrations remained low in patients with GETs, irrespective of the relative incidence of these cells in the mucosa and in tumours. The plasma values were not related/correlated to various clinico-pathological parameters. A malignant ghrelinoma was however an exception. The tumour released high total and active ghrelin concentrations into the blood circulation. The patient suffered from diarrhoea, hypothyroidism and diabetes mellitus, but it is not clear if these conditions were due to hyperghrelinaemia. The excretion U-MeImAA was increased in a few patients with GETs, but this increase was not always related to clinical symptoms.

In conclusion, ECL cells are an heterogeneous group according to VMAT-2 and HDC immunoreactivity. Ghrelin and obestatin are expressed in the same cells in the gastric mucosa, and a few of these cells display VMAT-2 immunoreactivity. Ghrelinoma is a new gastric tumour entity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 356
Keyword
Oncology, ECL cells, ghrelin cells, gastric endocrine tumours, VMAT-2, ghrelin, obestatin, HDC, U-MeImAA, Onkologi
Identifiers
urn:nbn:se:uu:diva-8804 (URN)978-91-554-7208-5 (ISBN)
Public defence
2008-05-28, Enghoffsalen, Entrance 50, University Hospital, Uppsala, 09:15
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Available from: 2008-05-06 Created: 2008-05-06 Last updated: 2010-12-20Bibliographically approved

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