MGMT, MYC and EBER Expression in Primary Diffuse Large B-cell Lymphoma of Central Nervous System

Introduction: Diffuse large B cell Lymphoma (DLBCL) is the most common type of primary central nervous system lymphoma (PCNSL). The molecular pathogenesis of PCNSL in immunocompetent individuals is different from that of immunocompromised ones and systemic lymphomas. Classification of patients according to prognostic molecular markers will help in targeted therapy. To date, only clinical prognostic factors such as age and immune status are introduced. The Recent rise in PCNSL incidence, especially in immunocompetent patients along with unknown pathogenesis and absence of molecular prognostic markers highlights the necessity of molecular studies in CNSLs. MGMT gene, normally present in all body tissues, protects DNA from the carcinogenic effect of alkylating agents and its mutation plays a role in the pathogenesis of PCNSL. Results of this study will aid in prognostic classification of PCNSL patients and predicting their response to alkylating agents as a new treatment modality. Methods: In this cross-sectional study, 78 patients with biopsy-proven CNS-DLBCL in the absence of systemic lymphoma at the time of diagnosis, were included in the study. Immunohistochemical (IHC) staining for MGMT and Ki67, FISH for MYC, and CISH for EBER were performed. The cases were subdivided into germinal center-type (GCB) and non-GCB according to CD10, BCL6, and MUM1 expression. MGMT, EBER, MYC and ki67 expression were compared between the two groups using SPSS software version 20. Results: PCNSL occurs in 5-7th decades of life (mean age: 54 years) with a predilection to male sex (M/F ratio 2:1). Most lesions are supratentorial and multifocality is seen in 12.5% of them. Most (78%) of tumors are of non-GCB type. Low C-MYC amplification is seen in 18% of cases. C-MYC amplification shows association with BCL2 and Ki67 expression. EBER is expressed in allimmunodeficient patients but in none of the immunocompetent ones. 2.5% (2 cases) are immunocompromised. One-third of the patients express MGMT. MGMT is expressed more in males and in MUM1-negative, GCB type, and CD10-positive tumors. Discussion: Majority of PCNSLs have a proliferative index of > =90%. C-MYC amplification is uncommon and none of PCNSLs shows high amplification. Unlike systemic DLBL, EBV does not play a role in PCNSLs, but is inevitable in CNS lymphomas of immunocompromised ones. MGMT expression is higher in less aggressive tumors, suggesting it as a prognostic factor. Patients with mutated MGMT (negative expression of MGMT on IHC) comprise about 67% of PCNSLs and will benefit from temozolomide.

Keywords:

Central netvous system , Diffuse large B cell Lymphoma (DLBCL) , CMYC , EBER , MGMT