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Gastrointestinal stromal tumors express the orexigen ghrelin
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
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2006 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, Vol. 13, no 3, 963-970 p.Article in journal (Refereed) Published
Abstract [en]

Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of the present study was to assess the relevance of this finding and identify a possible hormone production in these tumors. We chose to study the orexigen ghrelin and its receptor, since these patients are seldom cachexic, even in advanced disease stages. We investigated ghrelin expression by means of immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a well-characterized patient material. Expression of the growth hormone secretagogue receptor, the ghrelin receptor, was investigated in a subset of lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2 were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin, and its receptor, indicating the presence of autocrine/paracrine loops.

Place, publisher, year, edition, pages
2006. Vol. 13, no 3, 963-970 p.
Keyword [en]
gastrointestinal stromal tumors, neuroendocrine
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-83733DOI: 10.1677/erc.1.01201ISI: 000241924200022PubMedID: 16954444OAI: oai:DiVA.org:uu-83733DiVA: diva2:111641
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2012-02-16Bibliographically approved
In thesis
1. Pancreatic Endocrine Tumors and GIST - Clinical Markers, Epidemiology and Treatment
Open this publication in new window or tab >>Pancreatic Endocrine Tumors and GIST - Clinical Markers, Epidemiology and Treatment
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pancreatic endocrine tumors and gastrointestinal stromal tumors are rare. Evidence regarding prognostic factors, and in the former also treatment, is scarce.

We evaluated the survival and prognostic factors in a consecutive series of 324 patients with pancreatic endocrine tumors treated at a single institution. Radical surgery, WHO classification, TNM stage, age and Ki67 ≥2% emerged as independent prognostic factors. Having a non-functioning tumor was not an independent prognostic marker, and neither was hereditary tumor disease. We present the first evaluation of the newly proposed TNM staging system for these patients. A separate analysis of well-differentiated neuroendocrine carcinomas is reported, suggesting tumor size ≥5cm and Ki67 ≥2% as negative prognostic markers in this group.

The first 36 patients with advanced neuroendocrine tumors treated with temozolomide at our clinic were evaluated. The median time to progression was seven months. Fourteen percent showed partial regression and 53% stabilization of disease. Side effects were generally mild. Investigation of O6-methylguanine DNA methyltransferase revealed a low expression in a subset of tumors. Four out of five patients responding to treatment had tumors with low expression.

Concomitant expression of the orexigen ghrelin and its receptor in pancreatic endocrine tumors is demonstrated. No significant difference in mean plasma ghrelin between patients and controls were found, but elevated plasma ghrelin was seen in five patients.

We provide the first report of expression of ghrelin and its receptor in gastrointestinal stromal tumors. Concomitant expression was frequent, indicating the presence of an autocrine loop. The tumors also expressed the neuroendocrine marker synaptic vesicle protein 2. Together, these findings are suggestive of neuroendocrine features.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 64 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 267
Medicine, Pancreatic endocrine tumor, Gastrointestinal stromal tumor, Neuroendocrine, Multiple endocrine neoplasia type 1, Prognostic factors, Temozolomide, TNM staging, O6-methylguanine DNA methyltransferase, Growth hormone secretagogue receptor, Ghrelin, Medicin
urn:nbn:se:uu:diva-7937 (URN)978-91-554-6921-4 (ISBN)
Public defence
2007-09-07, Enghoffsalen, ing. 50, b.v., Akademiska Sjukhuset, Uppsala, 09:15 (English)
Available from: 2007-05-24 Created: 2007-05-24 Last updated: 2009-08-13Bibliographically approved

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Ekeblad, SaraLejonklou, Margareta HalinStålberg, PeterSkogseid, Britt
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