Co-expression of ghrelin and its receptor in pancreatic endocrine tumours.
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.


METHODS
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/m(2). 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.
Ekeblad
Sara
S
Department of Medical Sciences, University Hospitals, Uppsala, Sweden.
Lejonklou
Margareta Halin
MH
Grimfjärd
Per
P
Johansson
Térèse
T
Eriksson
Barbro
B
Grimelius
Lars
L
Stridsberg
Mats
M
Stålberg
Peter
P
Skogseid
Britt
B
D007516:Adenoma, Islet Cell / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016009:Chi-Square Distribution; D005260:Female; D015870:Gene Expression; D054439:Ghrelin; D006801:Humans; D007150:Immunohistochemistry; D007340:Insulinoma / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000737:chemistry / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D036361:Peptide Hormones / Q000032:analysis / Q000097:blood / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000235:genetics*; D054440:Receptors, Ghrelin; D015996:Survival Rate
D054439:Ghrelin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin