Isocitrate Dehydrogenase (IDH1) and p53 Mutations in Gliomas: A Cross-sectional Study from a Tertiary Care Hospital, Karnataka, India

Introduction: Gliomas, being the most common Central Nervous System (CNS) neoplasms, are broadly divided into astrocytomas, oligodendrogliomas and ependymomas. World Health Organisation (WHO) 2016 criteria incorporated Immunohistochemistry (IHC), molecular diagnostic techniques and histological tumour grading into its diagnostic criteria. Isocitrate Dehydrogenase (IDH1) mutations are commonly seen in young people with good prognostic implications. The detection of Tumor Protein53 (p53) mutations in gliomas and its association with the grade of the tumour can be used as a diagnostic, prognostic and therapeutic tool for better survival in affected individuals. IHC can be used as surrogate markers in detecting the mutational status of IDH1 and p53.

Aim: To study the expression of IDH1 and p53 mutations in gliomas and to evaluate its association with known clinicopathological variables.

Materials and Methods: This cross-sectional, retrospective, analytical study was conducted in the Department of Pathology at JSSAHER, Mysuru, Karnataka, India. The duration of the study was three years and 11 months, from October 2018 to September 2022. All histopathologically diagnosed glioma cases, who underwent surgery, were appropriately reviewed and graded. IHC was performed for the detection of IDH1mutational status and p53 expression. The tumour was labelled as, IDH1 positive with cytoplasmic staining and p53 positive when nuclear staining was observed in more than 5% of tumour cells. The p53 expression was further quantified in scores as low ≤8 and high >8 score. The associations of clinicopathological variables and the comparison of the scores of p53 mutation across various categories of gliomas were analysed statistically. The data was analysed using Statistical package for Social Sciences (SPSS) version 26.0.

Results: The mean age of the study participants was 15.3 years. A total of 35 cases (20 males and 15 females) were analysed. The maximum number of cases was in the age group of 31-40 years (n=13) followed by 41-50 years of age group (n=11). Three of them were seen in age less than 20 years. The male: female ratio was 1.33:1. Out of total cases, 20 cases showed IDH1 positivity, 12 cases showed high p53 expression and six cases demonstrated both, IDH1 positivity and high expression of p53. A statistically significant association (p-value=0.014) was seen between the grade of the tumour and p53 immunoreaction.

Conclusion: The present study of the detection of IDH1 and p53 mutations, could provide reliable information for improved tailoring of patient therapy as study revealed that, there was a significant association of p53 expression with the grade of the tumour with low expression in low grade gliomas and high p53 expression in high grade gliomas.