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弥漫性神经内分泌系统肿瘤中胰抑制素的出现。

The occurrence of pancreastatin in tumours of the diffuse neuroendocrine system.

作者信息

Bishop A E, Bretherton-Watt D, Hamid Q A, Fahey M, Shepherd N, Valentino K, Tatemoto K, Ghatei M A, Bloom S R, Polak J M

机构信息

Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.

出版信息

Mol Cell Probes. 1988 Sep;2(3):225-35. doi: 10.1016/0890-8508(88)90006-0.

Abstract

We have reported previously the localization of the 49 amino acid peptide pancreastatin to all identifiable endocrine cells of porcine gut, pancreas and adrenal, thyroid and pituitary glands. In this study, we have investigated the occurrence of pancreastatin in a series of human neuroendocrine tumours using an antibody to whole synthetic porcine pancreastatin. The most consistent immunostaining for pancreastatin was found in carcinoid tumours of ileum (four out of six), rectum (four out of six), ovary (two out of two) and lung (nine out of 10). Radioimmunoassay of tumour extracts showed that the concentrations of pancreastatin in ileal carcinoids were very high (mean 71.6, range 31.0-184.0 pmol g-1). The high rate of positivity in lung carcinoids contrasted sharply with the results of 10 pulmonary small cell carcinomas which displayed no immunoreactivity and contained minimal concentrations of pancreastatin (mean 2.0, range 0-6.0 pmol g-1). Extra-adrenal paragangliomas also contained pancreastatin (seven out of 10), but although radioimmunoassay detected peptide in phaeochromocytomas (mean 29.8, range 8.0-69.0 pmol g-1), immunocytochemistry did not. Porcine pancreastatin shows structural homology with bovine chromogranin A, an observation which has led to suggestions that chromogranin is a precursor for the peptide. More recently, a sequence homologous to porcine pancreastatin has been identified in the human chromogranin A molecule. In this study, immunostaining with an antiserum to human chromogranin gave positive results in most cases of each tumour type except the small cell carcinomas. The lack of consistent relationships between chromogranin and pancreastatin immunoreactivities may reflect the fact that the antiserum to pancreastatin was raised against the porcine peptide. When antibodies to human pancreastatin become available, the peptide may prove to be a more consistent marker for neuroendocrine tumours.

摘要

我们之前曾报道过,49个氨基酸的肽类物质胰抑制素定位于猪肠道、胰腺、肾上腺、甲状腺和垂体的所有可识别内分泌细胞中。在本研究中,我们使用针对全合成猪胰抑制素的抗体,对一系列人类神经内分泌肿瘤中胰抑制素的存在情况进行了研究。在回肠类癌(6例中有4例)、直肠类癌(6例中有4例)、卵巢类癌(2例均为阳性)和肺癌(10例中有9例)中发现了最一致的胰抑制素免疫染色。肿瘤提取物的放射免疫分析表明,回肠类癌中胰抑制素的浓度非常高(平均71.6,范围31.0 - 184.0 pmol g-1)。肺癌类癌的高阳性率与10例肺小细胞癌的结果形成鲜明对比,这些小细胞癌没有显示免疫反应,且胰抑制素浓度极低(平均2.0,范围0 - 6.0 pmol g-1)。肾上腺外副神经节瘤也含有胰抑制素(10例中有7例),但尽管放射免疫分析在嗜铬细胞瘤中检测到了该肽(平均29.8,范围8.0 - 69.0 pmol g-1),免疫细胞化学检测却未发现。猪胰抑制素与牛嗜铬粒蛋白A具有结构同源性,这一观察结果提示嗜铬粒蛋白是该肽的前体。最近,在人类嗜铬粒蛋白A分子中鉴定出了与猪胰抑制素同源的序列。在本研究中,除小细胞癌外,针对人类嗜铬粒蛋白的抗血清免疫染色在每种肿瘤类型的大多数病例中都得到了阳性结果。嗜铬粒蛋白和胰抑制素免疫反应性之间缺乏一致的关系,可能反映了针对猪肽产生的胰抑制素抗血清这一事实。当有针对人类胰抑制素的抗体可用时,该肽可能被证明是神经内分泌肿瘤更一致的标志物。

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