Document Type : Original Article
Authors
1
Department of Pathology, Oncopathology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
2
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
3
Department of Pathology, Oncopathology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
4
Department of Molecular Pathology and Cytogenetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
5
Department of Hematopathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
6
Department of Hematopathology and Molecular Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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.
Keywords