MGMT and p53 expressions in glioblastoma cases and comparison with prognostic factors

Glioblastoma is the most common and the most malignant primary tumor of the brain. O6-methylguanine-DNA-methyltransferase (MGMT) gene has been shown to be associated with improved outcome in glioblastoma and may be a predictive marker of sensitivity to alkylating agents. The aim of this study was to evaluate the correlation and prognostic significance of MGMT and p53 protein expression in patients with glioblastoma. Seventy-one patients, who were diagnosed with glioblastoma between the years 1995-2015 in the Pathology Department of Başkent University Faculty of Medicine were selected for the study. Paraffin embedded tumor tissues were immunohistochemically evaluated with monoclonal antibodies for MGMT and p53 protein. The correlation between the exprresion of MGMT and p53 protein and the survival was also examined. Only nuclear staining was considered positive for both antibodies. Immunoreacitivity was quantified by counting the stained nuclei expressed as a percentage of the positive cells. The immunoreactivity of the MGMT and the p53 protein was evaluated by estimating the fraction of positive cells, and a level of less than 10 % was regarded as negative, between %10 and % 50 as 1(+) and more than %50 as 2(+). In this study, the expression of MGMT and p53 was examined to eluciate the relationship between their immunostaining intensity. MGMT immunuhistochemistry was negative in 15 (%62,5) patients of p53 immunuhistochemistry negative group and in 30 (%63,8) p53 immunuhistochemistry positive group. There is no statistically significant correlation between MGMT and p53 expression. (p=1.00) We analysed the overall survival according to MGMT and p53 expression levels with Kaplan-Meier analysis. Mean survival time of group with p53 immunohistochemical expression level 1(+) is 24.26 months and group with 2(+) expression is 19.10 months. The mean survival time of p53 negative group is 8.00 months and this group has the lowest survival time among the other ones. There is no statistically significant relation between p53 expression levels and survival (p=0.16) Mean survival time of group with MGMT immunohistochemical expression level 1(+) is 9.29 months and group with 2(+) expression is 11.59 months. The mean survival time of MGMT negative group is 21.03 months and this group has the highest survival time among the other ones. There is no statistically significant relation between MGMT expression levels and survival (p=0.40). Since MGMT promoter methylation is a strong predictive marker for the response to alkylating chemotherapy agents, MGMT protein expression level is important for determining the patient who will get the temozolamide therapy that promotes the overall survival of the glioblastoma patients with poor prognosis. The mutation of p53 tumor supressor gene has an important role in the regulation of MGMT protein synthesis. The findings of our study support this relationship. However, because of the limited number of the cases, no statistically significant correlation between MGMT and p53 expression and the survival ratio was observed in our study. More cases with well known treatment protocoles should be enrolled to further studies which will be designed by immunohistochemical and genetic analysis.