Camilleri-Broët S, Camparo P, Mokhtari K, Hoang-Xuan K H, Martin A, Arborio M, Hauw J J, Raphaël M
Service d'Anatomie Pathologique, Hôtel Dieu, Paris, France.
Mod Pathol. 2000 Feb;13(2):158-65. doi: 10.1038/modpathol.3880030.
In contrast to primary central nervous system lymphomas (PCNSLs) that occur in immunocompetent patients, most of those that occur in immunosuppressed patients are associated with Epstein-Barr virus (EBV). BCL-2-related proteins either block or promote cell death, forming homo- or heterodimers with each other. LMP-1, EBV latent protein, has been shown to upregulate BCL-2 and BCL-XL. This observation suggests that these proteins may be involved in the transformation process of EBV-infected cells. Twenty-three cases of PCNSLs were studied: 12 of the patients were immunosuppressed, and 11 were immunocompetent. For all cases, we collected clinical information, histologic data, and immunophenotype and tested for the presence of EBV (EBER-1, LMP-1). Apoptosis was assessed by the TdT-mediated dUTP-biotin nick-end labeling method and quantified by image analysis. In three cases, electron microscopy was performed. The BCL-2 family proteins (BCL-2, BCL-X, MCL1, and BAX) and p53 expression were studied by immunohistochemistry on paraffin slides. All cases were classified as diffuse large B-cell lymphomas. PCNSLs in immunosuppressed patients were characterized by EBV association, necrosis, important gliosis, and numerous macrophages. There was no significant difference between the two groups regarding the TdT-mediated dUTP-biotin nick-end labeling staining (P = .08). In contrast, PCNSLs in immunosuppressed patients were shown to express high levels of BCL-2, BCL-X, and BAX in more than 80% of tumor cells in 7, 10, and 11 cases, respectively. In immunocompetent patients, only one case showed a high level of BCL-2 expression in more than 80% of the cells, whereas BCL-X and BAX were overexpressed in two cases. These differences are significant (P < .05). In contrast, there was no significant difference between the two groups in MCL-1 expression. Besides EBV association and necrosis, PCNSLs related to immunosuppression are characterized by an overexpression of BCL-2-related proteins, without dramatically modifying their susceptibility for apoptosis.
与发生在免疫功能正常患者中的原发性中枢神经系统淋巴瘤（PCNSL）不同，大多数发生在免疫抑制患者中的PCNSL与爱泼斯坦-巴尔病毒（EBV）相关。BCL-2相关蛋白要么阻断要么促进细胞死亡，它们相互形成同二聚体或异二聚体。EBV潜伏蛋白LMP-1已被证明可上调BCL-2和BCL-XL。这一观察结果表明，这些蛋白可能参与了EBV感染细胞的转化过程。对23例PCNSL病例进行了研究：12例患者免疫抑制，11例免疫功能正常。对于所有病例，我们收集了临床信息、组织学数据和免疫表型，并检测了EBV（EBER-1、LMP-1）的存在情况。通过TdT介导的dUTP生物素缺口末端标记法评估细胞凋亡，并通过图像分析进行定量。对3例病例进行了电子显微镜检查。通过石蜡切片免疫组织化学研究了BCL-2家族蛋白（BCL-2、BCL-X、MCL1和BAX）和p53表达。所有病例均分类为弥漫性大B细胞淋巴瘤。免疫抑制患者的PCNSL具有EBV相关性、坏死、明显的胶质增生和大量巨噬细胞的特征。两组在TdT介导的dUTP生物素缺口末端标记染色方面无显著差异（P = 0.08）。相比之下，免疫抑制患者的PCNSL在7例、10例和11例中分别有超过80%的肿瘤细胞表达高水平的BCL-2、BCL-X和BAX。在免疫功能正常的患者中，只有1例超过80%的细胞显示高水平的BCL-2表达，而BCL-X和BAX在2例中过表达。这些差异具有显著性（P < 0.05）。相比之下，两组在MCL-1表达方面无显著差异。除了EBV相关性和坏死外，与免疫抑制相关的PCNSL的特征是BCL-2相关蛋白的过表达，而没有显著改变其对细胞凋亡的易感性。
