Secretagogin is a new neuroendocrine marker in the human prostate
Secretagogin is a new neuroendocrine marker in the human prostate
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DOI：
10.1002/pros.20523
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发表时间：
2007-04-01
期刊：
影响因子：
2.8
通讯作者：
Torring, Niels
中科院分区：
文献类型：
--
作者：
Adolf, Katja;Wagner, Ludwig;Torring, Niels
背景前列腺癌（PCa）中的神经内分泌（NE）分化，由NE细胞分泌产物促进，似乎与肿瘤进展、不良预后和难治性疾病相关。我们最近报道了促分泌素，一种六EF手钙离子结合蛋白，作为一种新的NE标记物在肺和胃肠道类癌。本研究分析了促分泌素在正常和恶性前列腺组织中的表达。我们分析了87例福尔马林固定石蜡包埋（FFPE）良性增生（n = 10）和前列腺腺癌（n = 77）标本的连续切片中促分泌素、嗜铬粒蛋白A（CgA）、神经元特异性烯醇化酶（NSE）和突触素（SYN）的免疫反应性。通过共聚焦荧光显微镜检查分泌素、CgA和NSE的细胞内分布，并通过蛋白质印迹法鉴定8个样本中的分泌素。促分泌素在NE和NE分化的细胞中表达于细胞质和细胞核中，并且在良性前列腺和前列腺癌细胞中的上皮细胞中表达程度较低。82%（46/56）的良性前列腺组织和71%（48/68）的前列腺癌组织中分泌素染色，与NE标记物CgA和NSE共定位。前列腺癌组织中Secretagogin的表达与CgA（P < 0.001）、NSE（P < 0.048）及正常前列腺上皮中CgA（P < 0.028）均呈显著相关。促分泌素是前列腺中的新NE标记物，与NE标记物CgA、SYN和NSE相比具有更广泛的免疫反应性。促分泌素在前列腺腺癌中广泛表达，而不是在其他器官中的腺癌。
BACKGROUND. Neuroendocrine (NE) differentiation in prostate cancer (PCa), promoted by NE cell secreted products, appears to be associated with tumor progression, poor prognosis, and hormone-refractory disease. We recently reported secretagogin, a hexa-EF-hand Ca2+ binding protein, as a novel NE marker in carcinoid tumors of the lung and the gastrointestinal tract. The present study analyzes the expression of secretagogin in normal and malign prostate tissue.METHODS. We analyzed immunoreactivity for secretagogin, chromogranin A (CgA), neuron specific enolase (NSE), and synaptophysin (SYN) in consecutive sections from 87 formalin-fixed paraffin-embedded (FFPE) benign hyperplastic (n = 10) and prostate adenocarcinoma (n = 77) specimens. The intracellular distribution of secretagogin, CgA, and NSE was examined by confocal fluorescent microscopy, and we characterized secretagogin in eight samples by Western blotting.RESULTS. Secretagogin is cytoplasmic and nuclear expressed in NE and NE differentiated cells, and to a lesser extent in epithelial cells, in the benign prostate and prostate adenocarcinoma cells. Secretagogin stained 82% (46/56) of benign and 71% (48/68) of prostate adenocarcinomas and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P < 0.001) and NSE (P < 0.048) in prostate adenocarcinoma and to CgA in normal epithelium (P < 0.028).CONCLUSIONS. Secretagogin is a novel NE marker in the prostate with more extended immunoreactivity compared to the NE markers CgA, SYN, and NSE. Secretagogin is widely expressed in prostatic adenocarcinoma as opposed to adenocarcinomas in other organs.