title: Overexpression of BCL-2, BCL-X, and BAX in primary central nervous system lymphomas that occur in immunosuppressed patients.
abstract: 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.
authors.affiliation: Service d'Anatomie Pathologique, Hôtel Dieu, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Camilleri-Broët
authors.forename: P
authors.initials: P
authors.lastname: Camparo
authors.forename: K
authors.initials: K
authors.lastname: Mokhtari
authors.forename: K H
authors.initials: KH
authors.lastname: Hoang-Xuan
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Arborio
authors.forename: J J
authors.initials: JJ
authors.lastname: Hauw
authors.forename: M
authors.initials: M
authors.lastname: Raphaël
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D016867:Immunocompromised Host; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012367:RNA, Viral / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein