Arshad A Pandith, Iqbal Qasim, Wani Zahoor, Usma Manzoor, Ina Amin, Zahoor A Bhat, Parveen Shah and Abdul R Bhat
Sher-I-Kashmir Institute of Medical Sciences, India
University of Kashmir, India
Posters & Accepted Abstracts: J Cancer Sci Ther
Background: O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). The present study aimed to investigate methylation status of MGMT gene and in situ protein expression in malignant glioma patients of different histological types to analyze the clinical outcome using alkylating drugs and radiotherapy. Methods: Sixty-three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Results: MGMT gene methylation was detected in 38 (60.3%) cases and loss of protein expression was found in 36 cases (60%). Methylation status of MGMT and loss of protein expression showed very high concordance and significant association (p<0.0001). Both MGMT parameters showed a significantly higher OS and PFS (log rank p=.000). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with Hazard Ratio as 3.27 (95% CI; 0.96-10.73; p=0.048) and 7.17 (95% C.I; 2.01-25.5; p=0.002). Interestingly concordant MGMT methylation and lack of protein showed better response in patient subgroups treated with TMZ therapy as against those without (p<0.05). Conclusion: We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as favorable predictive factors for using TMZ therapy for better survival. We conclude both parameters of MGMT should be considered to benefit the glioma patients put on TMZ therapy.
Cancer Science & Therapy received 3968 citations as per Google Scholar report