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存活素在儿童髓母细胞瘤中的表达:一种可能的诊断和预后标志物。

Survivin expression in childhood medulloblastomas: a possible diagnostic and prognostic marker.

作者信息

Bodey Bela, Bodey Vivian, Siegel Stuart E, Kaiser Hans E

机构信息

Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, USA.

出版信息

In Vivo. 2004 Nov-Dec;18(6):713-8.

Abstract

Survivin is a member of the inhibitor of apoptosis gene family that is expressed in embryonic tissues during human ontogenesis and most human malignancies, but it is not present in the majority of normal adult tissues. Survivin is also a chromosomal passenger protein required for physiological cell divison. Survivin blocks apoptosis, via its BIR domain, by either directly or indirectly blocking the function of the members of the caspase cascade. The expression of this apoptosis inhibitor protein in medulloblastomas (MEDs) was examined for the first time. During the immunohistochemical study, a sensitive, four-step, alkaline phosphatase conjugated antigen detection technique was employed. The results did, in fact, demonstrate the presence of survivin in 10 to 50 per cent of medulloblastoma (MED) cells with medium intensity immunoreactivity (++, B) in this neuroectodermal brain tumor. These results indicate that survivin is probably not only a diagnostic marker, but also an important prognostic marker for MEDs/PNETs and may be useful in the future grading of malignancy in MEDs, much as grading is done today for astrocytomas (ASTRs). Furthermore, the almost exclusive neoplastic expression of survivin will allow development of new antineoplastic, immunotherapeutic strategies.

摘要

生存素是凋亡抑制基因家族的成员之一,在人类个体发育过程中的胚胎组织以及大多数人类恶性肿瘤中表达,但在大多数正常成人组织中不存在。生存素也是生理性细胞分裂所需的染色体乘客蛋白。生存素通过其杆状病毒IAP重复序列(BIR)结构域,直接或间接阻断半胱天冬酶级联反应成员的功能,从而阻止细胞凋亡。首次对髓母细胞瘤(MEDs)中这种凋亡抑制蛋白的表达进行了检测。在免疫组织化学研究中,采用了一种灵敏的、四步的、碱性磷酸酶偶联抗原检测技术。事实上,结果显示在这种神经外胚层脑肿瘤中,10%至50%的髓母细胞瘤(MED)细胞中存在生存素,免疫反应强度为中等(++,B)。这些结果表明,生存素可能不仅是一种诊断标志物,也是髓母细胞瘤/原始神经外胚层肿瘤(MEDs/PNETs)的重要预后标志物,并且未来可能有助于髓母细胞瘤的恶性分级,就像目前对星形细胞瘤(ASTRs)进行分级一样。此外,生存素几乎仅在肿瘤中表达这一特性将有助于开发新的抗肿瘤免疫治疗策略。

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