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Co-expression of ghrelin and its receptor in pancreatic endocrine tumours
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
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2007 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 66, no 1, 115-122 p.Article in journal (Refereed) Published
Abstract [en]

Objective 

Expression of ghrelin has been reported in pancreatic endocrine tumours, but data on ghrelin receptor protein expression are lacking. The aim of this study was to examine the ghrelin receptor, as well as ghrelin, in a selected series of these tumours, including multiple endocrine neoplasia 1 (MEN1) associated tumours, and to correlate data with clinical features including body mass index.

Design 

Immunohistochemical detection of ghrelin and its receptor was performed on frozen tissue from 31 tumours: 9 MEN1 and 22 sporadic. Twenty tumours were analysed by quantitative PCR. Plasma ghrelin was assessed in 26 patients.

Results 

Twenty-one (68%) of 31 tumours showed immunoreactivity for ghrelin (8/9 MEN1) and 19/20 expressed ghrelin mRNA. Ghrelin receptor protein was detected in 21/30 (70%) tumours (4/8 MEN1), and mRNA was detected in all analysed tumours. Insulinomas had significantly higher levels of receptor mRNA than other tumours. Five patients had elevated plasma ghrelin (> 2 SD above the control group mean). No significant difference in mean plasma ghrelin levels was found between patients (908 ± 569 ng/l) and controls (952 ± 164 ng/l). Mean BMI was 24·3 kg/m2. There was no association between ghrelin or receptor expression and survival.

Conclusions 

We report the first immunohistochemical data on expression of the ghrelin receptor in pancreatic endocrine tumours: 70% of tumours in our material. Concomitant ghrelin and receptor expression was seen in 50% of tumours, indicating an autocrine loop. Ghrelin was expressed in 68% of tumours (8/9 MEN1). Despite frequent ghrelin expression, elevated circulating ghrelin is rare in these patients.

Place, publisher, year, edition, pages
2007. Vol. 66, no 1, 115-122 p.
Keyword [en]
endocrine tumours, ghrelin receptor protein
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-22172DOI: 10.1111/j.1365-2265.2006.02695.xISI: 000242780500017PubMedID: 17201810OAI: oai:DiVA.org:uu-22172DiVA: diva2:49945
Available from: 2007-01-23 Created: 2007-01-23 Last updated: 2017-12-07Bibliographically 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 267
Keyword
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
Identifiers
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)
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Available from: 2007-05-24 Created: 2007-05-24 Last updated: 2009-08-13Bibliographically approved

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Ekeblad, SaraLejonklou, Margareta HalinEriksson, BarbroGrimelius, LarsStridsberg, MatsStålberg, PeterSkogseid, Britt

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