分泌粒蛋白是人类前列腺中的一种新的神经内分泌标志物。

Secretagogin is a new neuroendocrine marker in the human prostate.

作者信息

Adolf Katja, Wagner Ludwig, Bergh Anders, Stattin Pär, Ottosen Peter, Borre Michael, Birkenkamp-Demtröder Karin, Orntoft Torben Falck, Tørring Niels

机构信息

Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Center for Molecular Clinical Cancer Research (CMCC), Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej, Arhus, Denmark.

出版信息

Prostate. 2007 Apr 1;67(5):472-84. doi: 10.1002/pros.20523.

DOI:10.1002/pros.20523

PMID:17285592

Abstract

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 Ca(2+) 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.

摘要

背景

前列腺癌（PCa）中的神经内分泌（NE）分化由NE细胞分泌产物所促进，似乎与肿瘤进展、预后不良及激素难治性疾病相关。我们最近报道了分泌粒蛋白，一种具有六个EF手型结构的Ca(2+)结合蛋白，作为肺和胃肠道类癌肿瘤中的一种新型NE标志物。本研究分析了分泌粒蛋白在正常及恶性前列腺组织中的表达情况。

方法

我们分析了来自87例福尔马林固定石蜡包埋（FFPE）的良性增生（n = 10）和前列腺腺癌（n = 77）标本连续切片中分泌粒蛋白、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粒蛋白、CgA和NSE的细胞内分布，并通过蛋白质免疫印迹法对8个样本中的分泌粒蛋白进行了表征。

结果

在良性前列腺和前列腺腺癌细胞中，分泌粒蛋白在NE及NE分化细胞的细胞质和细胞核中表达，在上皮细胞中的表达程度较低。分泌粒蛋白在82%（46/56）的良性前列腺组织和71%（48/68）的前列腺腺癌中呈阳性染色，并与NE标志物CgA和NSE共定位。在前列腺腺癌中，分泌粒蛋白的表达与CgA（P < 0.001）和NSE（P < 0.048）显著相关，在正常上皮中与CgA相关（P < 0.028）。