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O-6-Methylguanine-Dna Methyltransferase, C-Myc, and Eber Status in Diffuse Large B-Cell Lymphoma of Central Nervous System Publisher



Sadeghipour A1 ; Mohagheghian H2 ; Movahedinia S1, 3 ; Kosari F4 ; Monabati A5
Authors
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Authors Affiliations
  1. 1. Department of Pathology, Oncopathology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Molecular Pathology and Cytogenetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Hematopathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Hematopathology and Molecular Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Source: International Journal of Molecular and Cellular Medicine Published:2024


Abstract

Diffuse Large B-cell Lymphoma (DLBCL), the most common type of primary central nervous system lymphoma (PCNSL), is a rare aggressive subtype of DLBCL with a poorly understood biology. This study aimed to investigate the prevalence of O-6-Methylguanine-DNA Methyltransferase (MGMT), C-MYC and Epstein-Barr virus Encoded RNA (EBER) positivity in CNS-DLBCLs. Using tissue microarray method, formalin-fixed paraffin-embedded blocks of 76 cases of confirmed PCNS-DLBCL and 2 cases of immunodeficiency-related CNS DLBCL were examined for EBER and C-MYC by chromogenic in situ hybridization (CISH), and for MGMT, CD10, BCL2, BCL6, MUM1 and Ki67 by Immunohistochemistry (IHC). The results were analyzed in association with histopathologic and demographic characteristics. The majority of the tumors were of non-germinal center B-cell (non-GCB) type. Loss of MGMT expression on IHC, as a surrogate marker of MGMT methylation, was detected in about 68.9% of PCNSLs. Preserved MGMT expression was found to occur more frequently in males and in MUM1-negative and GCB-type tumors. EBER positivity was exclusively seen in immunodeficient cases. Low C-MYC amplification was detected in 18% of cases and showed association with BCL2 and Ki67 expression. We concluded that loss of MGMT expression is a common phenomenon in PCNSLs. Epstein-Barr virus (EBV) may not be commonly detected in PCNS-DLBCL as frequently as in systemic DLBCL, but its expression is inevitable in CNS-DLBCLs of immunocompromised ones. Maintained MGMT expression is associated with less aggressive histopathologic features. Further studies are warranted to confirm the prognostic significance of loss of MGMT expression in PCNSLs and its potential use for predicting therapeutic response to alkylating agents in PCNSLs. © The Author(s). Publisher: Babol University of Medical Sciences This work is published as an open access article distributed under the terms of the Creative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by-nc/4). Non-commercial uses of the work are permitted, provided the original work is properly cited.