[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

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

Mod Pathol. 2000 Feb;13(2):158-65. doi: 10.1038/modpathol.3880030.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / virology
  • Female
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunocompromised Host*
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / virology
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / virology
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • RNA, Viral / metabolism
  • Viral Matrix Proteins / metabolism
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • BAX protein, human
  • BCL2L1 protein, human
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr virus encoded RNA 1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Viral
  • Viral Matrix Proteins
  • bcl-2-Associated X Protein
  • bcl-X Protein