Overexpression of BCL-2, BCL-X, and BAX in primary central nervous system lymphomas that occur in immunosuppressed patients

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 protei ns either block or promote cell death, forming homo- or heterodimers with e ach other. LMP-I, EBV latent protein, has been shown to upregulate BCL-2 an d 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 immunosu ppressed, and 11 were immunocompetent. For all cases, we collected clinical information, histologic data, and immunophenotype and tested for the prese nce 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 immunohistochemi stry on paraffin slides. All cases were classified as diffuse large B-cell lymphomas. PCNSLs in immu nosuppressed patients were characterized by EBV association, necrosis, impo rtant gliosis, and numerous macrophages. There was no significant differenc e between the two groups regarding the TdT-mediated dUTP-biotin nick-end la beling 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 p atients, 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. T hese differences are significant (P < .05). In contrast, there was no signi ficant difference between the two groups in MCL-1 expression. Besides EBV a ssociation and necrosis, PCNSLs related to immunosuppression are characteri zed by an overexpression of BCL-2-related proteins, without dramatically mo difying their susceptibility for apoptosis.