Clinicopathological Implications of IDH1 Mutation and Ki-67 Expression Across WHO Grades of Gliomas: Insights from a Prospective Observational Study

Abstract

Background & Objective: Gliomas are heterogeneous central nervous system tumors with variable outcomes. Accurate classification using histopathological and molecular markers, such as IDH1 R132H mutation and Ki-67 index, is essential. This study evaluated their distribution across glioma grades and correlation with clinicopathological parameters. Methods: This prospective observational study included 90 histologically confirmed glioma cases. Hematoxylin and eosin (H&E)-stained sections were graded according to WHO 2021 criteria. Immunohistochemistry was used to assess IDH1 R132H mutation status and Ki-67 labeling index. Associations between variables were analyzed using chi-square and logistic regression. Results: Astrocytomas (55/90, 61.1%) and glioblastomas (24/90, 26.7%) were the most common tumor types. IDH1 R132H mutation was detected in 65/90 cases (72.2%). Grade-wise, mutation positivity was highest in grade II (28/28, 100%), followed by grade I (8/9, 88.9%) and grade III (20/26, 76.9%), whereas grade IV glioblastomas showed significantly lower positivity (9/27, 33.3%). Ki-67 expression increased with tumor grade, with >20% expression in 26/27 grade IV tumors (96.3%). A significant inverse correlation was observed between IDH1 mutation status and Ki-67 level (P < 0.0001). Logistic regression showed that younger age was significantly associated with IDH1 mutation (P = 0.001), while IDH1 wild-type status correlated with older age (P = 0.024). Conclusion: IDH1 R132H mutation and Ki-67 index correlate with glioma grade and age, supporting their routine use in classification. In the absence of survival data, the present results reflect clinicopathological associations rather than validated prognostic predictions; prospective studies incorporating survival outcomes are needed to confirm the prognostic utility of these markers.