Gliomas - An experience based on molecular markers

Abstract

Background: Gliomas account for 45% of all intracranial tumors. Newer technologies have allowed deeper genetic and epigenetic analysis leading to the discovery of IDH (Isocitrate dehydrogenase) mutations and their association with ATRX (alpha-thalassemia/mental retardation syndrome X-linked) and p53, for better diagnosis and prognosis. In this study, we analysed their expression and correlated with various clinicopathological parameters. A follow up to prognosticate gliomas based on the molecular findings is also attempted. Materials and Method: During last 5 years both retrospective and prospective cases were included in the study. Immunohistochemistry for IDH1, ATRX, and p53 was done and reported based on intensity and percentage of tumor cells expressing the markers. Results: A total of 53 cases of gliomas were included, excluding primary glioblastomas and ependymomas. The patient s age ranged from 10 to 53 years. The male to female ratio was 1.3:1. IDH1 positivity was seen in 88% of diffuse astrocytoma, 80% of anaplastic astrocytoma, 90% of oligodendroglioma, 60% of anaplastic oligodendroglioma, and 54% of glioblastoma. A significant association was seen between positive IDH1 expression and low-grade gliomas (p = 0.028). A combined analysis of expression of IDH1 and ATRX versus IDH1, ATRX, and p53 with WHO grade showed a statistically significant association. A follow-up of 32 patients was available. Out of 24 IDH1+ (positive) cases, 22 patients had a median survival of 21.5 months (92%). Out of 8 IDH1- (negative) cases, 5 had a median survival of 15.8 months (62%). Conclusion: Gliomas expressing IDH1 mutation show improved survival of patients. Combined analysis of IDH1, ATRX, and p53 has diagnostic and prognostic significance. For routine cases of gliomas, a combination of IDH1 and ATRX are sufficient; however, the use of p53 is recommended for further prognostication and for possible targeted therapy in the future.