Ekeblad Sara, Lejonklou Margareta Halin, Grimfjärd Per, Johansson Térèse, Eriksson Barbro, Grimelius Lars, Stridsberg Mats, Stålberg Peter, Skogseid Britt
Department of Medical Sciences, University Hospitals, Uppsala, Sweden.
Clin Endocrinol (Oxf). 2007 Jan;66(1):115-22. doi: 10.1111/j.1365-2265.2006.02695.x.
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.
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.
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.
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.
已有报道称胃饥饿素在胰腺内分泌肿瘤中表达，但缺乏胃饥饿素受体蛋白表达的数据。本研究的目的是在一系列此类肿瘤（包括与多发性内分泌肿瘤1型（MEN1）相关的肿瘤）中检测胃饥饿素受体以及胃饥饿素，并将数据与包括体重指数在内的临床特征相关联。
对31个肿瘤的冷冻组织进行胃饥饿素及其受体的免疫组化检测：9个MEN1相关肿瘤和22个散发性肿瘤。对20个肿瘤进行定量PCR分析。对26例患者的血浆胃饥饿素进行评估。
31个肿瘤中有21个（68%）对胃饥饿素呈免疫反应性（8/9个MEN1相关肿瘤），20个中有19个表达胃饥饿素mRNA。在21/30（70%）个肿瘤（4/8个MEN1相关肿瘤）中检测到胃饥饿素受体蛋白，在所有分析的肿瘤中均检测到mRNA。胰岛素瘤的受体mRNA水平显著高于其他肿瘤。5例患者血浆胃饥饿素升高（高于对照组平均值2个标准差以上）。患者（908±569 ng/l）和对照组（952±164 ng/l）的平均血浆胃饥饿素水平无显著差异。平均体重指数为24.3 kg/m²。胃饥饿素或受体表达与生存率之间无关联。
我们报告了关于胃饥饿素受体在胰腺内分泌肿瘤中表达的首批免疫组化数据：我们材料中的肿瘤有70%表达。50%的肿瘤同时出现胃饥饿素和受体表达，表明存在自分泌环。68%的肿瘤（8/9个MEN1相关肿瘤）表达胃饥饿素。尽管胃饥饿素表达频繁，但这些患者中循环胃饥饿素升高的情况罕见。
