Gould V E, Wiedenmann B, Lee I, Schwechheimer K, Dockhorn-Dworniczak B, Radosevich J A, Moll R, Franke W W
Am J Pathol. 1987 Feb;126(2):243-57.
Synaptophysin is an integral membrane glycoprotein originally isolated from presynaptic vesicles of bovine neurons. The authors have studied a wide spectrum of neuroendocrine (NE) neoplasms by immunofluorescence microscopy on cryostat sections of freshly frozen tissues using a monoclonal antibody to this protein (SY 38). Without exception, they found the identical--or a very similar--protein expressed in all neuroblastomas, ganglioneuroblastomas, ganglioneuromas, pheochromocytomas, and paragangliomas studied. In these "neural" type NE neoplasms, synaptophysin was coexpressed with neurofilament proteins. Synaptophysin was also demonstrated in NE neoplasms of "epithelial" type in which it was predominantly coexpressed with cytokeratins and desmoplakin. It was invariably found in all variants of islet cell neoplasms and in all medullary thyroid carcinomas. Synaptophysin was also demonstrated in several adenomas of the hypophysis and parathyroids, in the majority of carcinoids of the bronchopulmonary and gastrointestinal tracts, and in many, though not all, NE carcinomas of the same sites, and of the skin. Conversely, SY 38 did not immunostain any of a large number of benign and malignant non-NE epithelial neoplasms; nor was any immunostaining obtained in a group of mesenchymal tumors. It is remarkable that SY 38 did not immunostain a number of malignant melanomas, including several that were immunostained for neuron-specific enolase (NSE) and several neuropeptides. Parallel studies conducted on conventionally fixed, paraffin-embedded tissue sections immunostained by the use of the avidin-biotin complex technique yielded very similar results. The findings indicate that synaptophysin is expressed in the whole range of NE neoplasms without detectable relation to the expression of other NE markers such as NSE, serotonin, and neuropeptides. Nor could the expression of synaptophysin by these tumors be correlated with their epithelial and/or neural cytoskeletal characteristics, their clinical aggressiveness, or the presence or absence of endocrinologic abnormalities. While the consistent expression of synaptophysin by the "neural" type of NE neoplasms would seem predictable its presence in diverse benign and malignant NE tumors of "epithelial" type is remarkable. It is concluded that synaptophysin is a significant as well as novel NE marker, and the use of antibody SY 38 as a broad range marker for the study and diagnosis of NE neoplasms is proposed.
突触素是一种整合膜糖蛋白，最初从牛神经元的突触前小泡中分离出来。作者使用针对该蛋白的单克隆抗体（SY 38），通过对新鲜冷冻组织的低温切片进行免疫荧光显微镜检查，研究了广泛的神经内分泌（NE）肿瘤。无一例外，他们发现在所有研究的神经母细胞瘤、神经节神经母细胞瘤、神经节神经瘤、嗜铬细胞瘤和副神经节瘤中都表达了相同的——或非常相似的——蛋白。在这些“神经”型NE肿瘤中，突触素与神经丝蛋白共表达。突触素也在“上皮”型NE肿瘤中得到证实，在其中它主要与细胞角蛋白和桥粒斑蛋白共表达。在所有胰岛细胞瘤变体和所有甲状腺髓样癌中均始终发现突触素。突触素也在垂体和甲状旁腺的一些腺瘤、大多数支气管肺和胃肠道类癌以及许多（尽管不是全部）相同部位和皮肤的NE癌中得到证实。相反，SY 38对大量良性和恶性非NE上皮性肿瘤均未进行免疫染色；在一组间叶组织肿瘤中也未获得任何免疫染色。值得注意的是，SY 38对一些恶性黑色素瘤未进行免疫染色，包括一些对神经元特异性烯醇化酶（NSE）和几种神经肽进行免疫染色的黑色素瘤。对使用抗生物素蛋白-生物素复合物技术进行免疫染色的常规固定、石蜡包埋组织切片进行的平行研究得出了非常相似的结果。这些发现表明，突触素在整个NE肿瘤范围内均有表达，与其他NE标志物如NSE、血清素和神经肽的表达无明显关联。这些肿瘤中突触素的表达也与它们的上皮和/或神经细胞骨架特征、临床侵袭性或内分泌异常的有无无关。虽然“神经”型NE肿瘤中突触素的一致表达似乎可以预测，但它在“上皮”型各种良性和恶性NE肿瘤中的存在却很显著。结论是突触素是一种重要且新颖的NE标志物，并建议使用抗体SY 38作为研究和诊断NE肿瘤的广泛标志物。
