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免疫功能正常的老年患者中与 Epstein-Barr 病毒相关的原发性中枢神经系统淋巴瘤:潜伏膜蛋白 1 癌基因缺失和 EBNA-2 株型分析。

Epstein-Barr virus-associated primary central nervous system lymphomas in immunocompetent elderly patients: analysis for latent membrane protein-1 oncogene deletion and EBNA-2 strain typing.

机构信息

Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

出版信息

J Neurooncol. 2010 Nov;100(2):271-9. doi: 10.1007/s11060-010-0191-z. Epub 2010 May 9.

Abstract

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of primary central nervous system lymphomas (PCNLs) in immunocompetent hosts. To investigate the role of EBV in the pathogenesis of PCNLs in immunocompetent hosts, this study assessed six PCNL cases (elderly male immunocompetent patients; age ≥60 years) histologically and immunohistochemically, and an EBV genetic study was performed. Histologically, all cases were diagnosed as diffuse large B-cell lymphoma with extensive necrosis. In all six cases, PCNL cells showed immunohistochemical positivity for latent membrane protein 1 (LMP-1) and Epstein-Barr nuclear 2 (EBNA2). Lymphoma cells also showed positive signals for EBV-encoded small RNAs (EBERs) on in-situ hybridization. EBV subtyping-PCR analysis demonstrated that one case was EBNA 2B type and the other five cases were EBNA 2A type, and two cases were EBV wild-type and four cases showed 30-bp LMP-1 deletion by PCR analysis. It is therefore possible that LMP gene deletion or EBNA-2 strain type are important in the tumorigenesis of EBV-positive PCNLs. In addition, EBV-positive PCNLs in immunocompetent hosts may be related to immunological deterioration derived from the aging process.

摘要

EBV 病毒已被认为与免疫功能正常宿主的原发性中枢神经系统淋巴瘤(PCNL)的发病机制有关。为了研究 EBV 在免疫功能正常宿主 PCNL 发病机制中的作用,本研究对 6 例 PCNL 病例(老年男性免疫功能正常患者;年龄≥60 岁)进行了组织学和免疫组织化学评估,并进行了 EBV 基因研究。组织学上,所有病例均被诊断为弥漫性大 B 细胞淋巴瘤,伴有广泛坏死。在所有 6 例病例中,PCNL 细胞均表现出潜伏膜蛋白 1(LMP-1)和 EBV 核抗原 2(EBNA2)的免疫组织化学阳性。原位杂交显示淋巴瘤细胞也呈 EBV 编码的小 RNA(EBERs)阳性信号。EBV 亚型 PCR 分析表明,1 例为 EBNA 2B 型,5 例为 EBNA 2A 型,2 例为 EBV 野生型,4 例为 PCR 分析显示 30-bp LMP-1 缺失。因此,LMP 基因突变或 EBNA-2 株型可能在 EBV 阳性 PCNL 的肿瘤发生中起重要作用。此外,免疫功能正常宿主的 EBV 阳性 PCNL 可能与衰老过程中免疫功能下降有关。

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