O6-methylguanine DNA methyltransferase gene promoter methylation status in glioblastoma and its correlation with other prognostic markers

Abstract

Glioblastoma is the most frequent and malignant brain tumor with most patients dying within 1 year after diagnosis. O6-Methylguanine DNA methyltransferase (MGMT) is implicated as a major predictive factor for treatment response to alkylating agents including temozolomide (TMZ). In general, epigenetic silencing of the MGMT gene by promoter methylation is associated with loss of MGMT protein expression. We investigated the correlation between MGMT protein expression and MGMT methylation status and the prognostic relevance of TP53 and Ki-67 in a series of glioblastomas. A total of twenty-eight patients between 2008 and 2011 were included in this study. Nineteen patients (68%) showed nuclear TP53 immunopositivity, and mean Ki-67 index was 27%. Immunohistochemistry for MGMT protein revealed high expression (>30% positive cells) in 11 tumors, and low expression (≤30% positive cells) in 17 tumors. There was a good correlation between immunoreactivity for MGMT protein, Ki-67 index and tumor extent. MGMT promoter methylation as well as MGMT protein expression was completely uncorrelated to survival prediction; neither TP53 nor Ki-67 were correlated to survival. Our study confirms the role of the Ki-67 index and the extent of tumor as two important factors associated with prognosis of glioblastoma. In contrast, MGMT protein expression as well as the MGMT promoter methylation status does not provide prognostically relevant information.