Ekeblad Sara, Nilsson Bengt, Lejonklou Margareta Halin, Johansson Térèse, Stålberg Peter, Nilsson Ola, Ahlman Håkan, Skogseid Britt
Department of Medical Sciences, University Hospital, 75185 Uppsala, Sweden.
Endocr Relat Cancer. 2006 Sep;13(3):963-70. doi: 10.1677/erc.1.01201.
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.
少数胃肠道间质瘤（GIST）病例中已报道有神经内分泌标志物突触小泡蛋白2（SV2）的表达。本研究的目的是评估这一发现的相关性，并确定这些肿瘤中可能存在的激素产生情况。由于这些患者即使在疾病晚期也很少出现恶病质，我们选择研究促食欲素胃饥饿素及其受体。我们通过免疫组织化学方法，对来自特征明确的患者材料的22例GIST的冰冻切片或石蜡包埋切片进行胃饥饿素表达研究。在一部分病变中研究了生长激素促分泌素受体（即胃饥饿素受体）的表达。在6个肿瘤中，通过实时定量PCR分析了胃饥饿素、胃饥饿素受体和SV2的mRNA水平。22个肿瘤中有17个显示出胃饥饿素免疫反应性。10个肿瘤中有5个对胃饥饿素受体呈免疫反应性，并且所有这些肿瘤均共表达胃饥饿素。所有肿瘤均表达胃饥饿素、胃饥饿素受体和SV2 mRNA。GIST经常表达SV2、胃饥饿素及其受体，表明存在自分泌/旁分泌环。
