Dynamics of IDH1 Mutation and Protein Expression Between Primary and Recurrent Gliomas and Their Prognostic Significance
Wei Yu, Siyu Guo, Beibei Liu, Qichun WeiBackground
Isocitrate dehydrogenase 1 (IDH1) mutation is a key molecular marker in gliomas and is generally associated with favorable prognosis. However, its dynamic changes and prognostic significance during tumor recurrence remain incompletely understood.
Methods
We conducted a retrospective analysis of 42 patients with paired primary and recurrent glioma samples. IDH1 mutation status was determined by PCR, and the expression of IDH1 R132H protein was evaluated using a semiquantitative scoring system ranging from negative (−) to strongly positive (+++) based on expression intensity by immunohistochemistry (IHC). Changes in molecular features and WHO grade were analyzed, and their associations with progression‐free survival (PFS), overall survival (OS), and postrecurrence survival (PRS) were evaluated using Cox regression models.
Results
IDH1 mutation status remained largely stable between primary and recurrent tumors, with most patients retaining their original genotype. In contrast, WHO grade progression was observed in 45.2% of cases, indicating ongoing tumor evolution. IDH1 R132H protein expression exhibited dynamic changes, with both upregulation and downregulation detected at recurrence. In primary tumors, IDH1 mutation was independently associated with improved PFS (HR = 0.351, p = 0.016), whereas higher IDH1 R132H expression was associated with improved OS (HR = 0.371, p = 0.032). In recurrent tumors, IDH1 mutation showed a trend toward inferior PRS, although this association did not reach statistical significance, suggesting that the prognostic relevance of IDH1 alterations may vary during glioma evolution.
Conclusions
Although IDH1 mutation remains largely stable during glioma progression, its prognostic associations may vary between primary and recurrent disease. IDH1 R132H protein expression also shows dynamic changes and may provide complementary prognostic information. These exploratory findings support integrating genetic and protein‐level biomarkers when evaluating glioma progression and warrant validation before informing the clinical application of IDH inhibitors.