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.

Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study

“…In conclusion, as Sarma et al reported, 20,33 we think combined IHC markers for IDH1R132H, P53, and ATRX significantly improve the molecular classification of adult diffuse gliomas in daily practice, especially in low resources area where molecular tests are not widely available. The IHC results can be used as a guide for the selection of limited cases for co-deletion testing.…”

“…Positive mutation has a considerable favorable impact on diffuse glioma behavior, irrespective of any other marker 15 . IDH mutation is frequent in histological grade 2and 3 astrocytomas 18,19 and is seen in about 70% to 90% of them as well as about 80% of oligodendrogliomas 20 …”

“…They presented 4/42 cases of co-deleted glioma with difficult morphology for oligodendroglioma. In such cases, ATRX retention could be used as a supportive role for oligodendroglial linage in IDH mutant glioma where advanced techniques such as FISH are not available, 20 but it should be mentioned that it is not a substitution.…”

Gemistocytic Differentiation in Isocitrate Dehydrogenase Mutant Astrocytomas: A Histopathological and Survival Analysis

“…IDH mutant Astrocytoma is an infiltrative glioma of neoplastic astrocytes that diffusely invade glial tissue. Its diagnosis is supported by mutations of p53 and ATRX genes [3,4]. IDH mutation analysis is now a prerequisite for diagnosing an Astrocytoma, and research shows that these mutations appear to confer a significant survival advantage over their wild-type counterparts [5][6][7][8][9].…”