MPTH-07GLIOBLASTOMAS: CORRELATION OF MGMT GENE PROMOTER METHYLATION WITH CLINICO-PATHOLOGICAL AND MOLECULAR PARAMETERS

Abstract

Methylation of O6-methylguanine DNA methyltransferase (MGMT) is one of the predictive and prognostic markers of glioblastomas (GBMs). In this study, GBMs have been evaluated for the same and correlated with other clinicopathological and molecular parameters. MATERIALS AND METHODS: Diagnosed cases of GBM, during the period of June 2014 to December 2014 in the Department of Pathology of our Institute, wherein they have been evaluated for MGMT methylation by methylation specific polymerase chain reaction, IDH1R132H and p53 protein expression by immunohistochemistry and EGFR gene amplification by fluorescence in-situ hybridisation formed the study sample. Statistical correlation was done by Chi-square and Fischer's exact, using IBM SPSS Software 16 version. RESULTS: A total of 97 cases of GBM formed the study sample with age range of 20-75 years (mean age:49.76 years) and male: female ratio of 3.2:1 (M:74;F:23).Cerebral hemispheric location was commonest (frontal:35%; temporal:43 & parietal:19%). 46 (47.4%) cases were MGMT methylated (low methylation: 10) and 51 were unmethylated. 23 out of 84 cases (27.4%) were EGFR amplified; 10 cases (10.3%) were positive for IDH1R132H; 16 showed loss of ATRX protein expression (of which 7 were IDH1R132H positive; while the other 3 IDHR132H positive cases showed retained ATRX protein). Of the 46 MGMT methylated cases, 10 were EGFR amplified (10 out of 23 EGFR amplified cases were MGMT methylated); 5 were IDH1R132H positive and 6 showed loss of ATRX expression. None of the molecular markers showed any correlation for the histological features of calcification and necrosis (neither for pseudopalisading or confluent). CONCLUSIONS: MGMT was methylated in 47.4%of GBMs and had no significant statistical correlation with EGFR gene amplification, IDH1R132H mutation, ATRX protein expression and other histomorphological features. This study did not identify any surrogate marker for MGMT promoter methylation.