Stridsberg M, Eriksson B, Lundqvist G, Skogseid B, Wilander E, Oberg K
Department of Clinical Chemistry, University Hospital of Uppsala, Sweden.
Regul Pept. 1995 Jan 26;55(2):119-31. doi: 10.1016/0167-0115(94)00097-h.
Although IAPP was first discovered and isolated from amyloid deposits in an endocrine pancreatic tumour (EPT), surprisingly few reports have investigated the potential use of IAPP as a marker for neuroendocrine tumour growth. In this study we present results from plasma measurements of IAPP in 102 patients with neuroendocrine tumours. Four of 35 patients (11%) with midgut carcinoid tumours, but none of the patients (4 and 5, respectively) with lung carcinoids or with rectal carcinoids displayed elevated plasma levels of IAPP. Five of 31 patients (16%) with sporadic EPT and 3 of 27 patients (11%) with EPT and multiple endocrine neoplasia type 1 syndrome disclosed elevated IAPP levels. Within the different syndromes, 1/11 individuals with insulinoma, 2/16 with gastrinoma, 0/2 with glucagonoma, 0/3 with VIPoma and 5/26 with non-functioning tumours showed elevated plasma levels of IAPP. In two patients, the plasma IAPP levels were extremely elevated. These patients also exhibited altered glucose homeostasis. In response to a standardised mixed meal test, IAPP increased in parallel to the insulin, pancreatic polypeptide, gastrin and glucose responses. In MEN1 patients with hypercalcaemia due to increased secretion of parathyroid hormone, the plasma levels of IAPP were significantly higher before than after surgical removal of the parathyroid adenomas. However in normocalcaemic patients, no correlation between the blood calcium and plasma IAPP levels was found. Immunocytochemical staining of tumour tissue showed that 9/13 (69%) of insulin producing tumours, 4/14 (29%) of non-functioning tumours and 1/9 (11%) of gastrin producing tumours were IAPP immunoreactive. Amyloid deposits were always IAPP immunoreactive. In conclusion, increased circulating levels of IAPP occurred in 12% of 102 patients with neuroendocrine tumours. In 2 patients with extremely elevated plasma levels of IAPP, effects on glucose homeostasis were recorded. Thus, IAPP may be useful as an additional marker for neuroendocrine tumour growth in selected cases.
尽管胰岛淀粉样多肽（IAPP）最初是从内分泌胰腺肿瘤（EPT）的淀粉样沉积物中发现并分离出来的，但令人惊讶的是，很少有报告研究IAPP作为神经内分泌肿瘤生长标志物的潜在用途。在本研究中，我们展示了102例神经内分泌肿瘤患者血浆IAPP测量的结果。35例中肠类癌肿瘤患者中有4例（11%）血浆IAPP水平升高，但肺癌类癌或直肠类癌患者（分别为4例和5例）均未出现血浆IAPP水平升高。31例散发性EPT患者中有5例（16%）以及27例患有1型多发性内分泌腺瘤综合征的EPT患者中有3例（11%）IAPP水平升高。在不同综合征中，11例胰岛素瘤患者中有1例、16例胃泌素瘤患者中有2例、2例胰高血糖素瘤患者中无、3例血管活性肠肽瘤患者中无以及26例无功能性肿瘤患者中有5例血浆IAPP水平升高。在2例患者中，血浆IAPP水平极度升高。这些患者还表现出血糖稳态改变。在标准化混合餐试验中，IAPP与胰岛素、胰多肽、胃泌素和葡萄糖反应平行升高。在因甲状旁腺激素分泌增加导致高钙血症的MEN1患者中，甲状旁腺腺瘤手术切除前血浆IAPP水平显著高于切除后。然而，在血钙正常的患者中，未发现血钙与血浆IAPP水平之间存在相关性。肿瘤组织的免疫细胞化学染色显示，13例胰岛素分泌肿瘤中有9例（69%）、14例无功能性肿瘤中有4例（29%）以及9例胃泌素分泌肿瘤中有1例（11%）对IAPP呈免疫反应性。淀粉样沉积物始终对IAPP呈免疫反应性。总之，102例神经内分泌肿瘤患者中有12%出现循环IAPP水平升高。在2例血浆IAPP水平极度升高的患者中，记录到了对血糖稳态的影响。因此，在某些特定情况下，IAPP可能作为神经内分泌肿瘤生长的附加标志物有用。
