Correlation between Isocitrate Dehydrogenase Mutation and Immunohistochemical Expression of DNA Mismatch Repair Proteins in the Prognosis of Gliomas

Saeed, Nelly Mohamed; Rashed, Hayam; Hussein, Samia; Al-Karamany, Amira S; Elmesallamy, Wael; Waley, Ahmad Barakat; Obay, Ahmed A; Gharieb, Shimaa A; Amgd, Kareem; Ibrahim, Sara Mohammed; Abdelhamid, Mohamed I; Khamis, Tarik; Mohamed, Asmaa Hussein

doi:10.31557/APJCP.2025.26.4.1447

Correlation between Isocitrate Dehydrogenase Mutation and Immunohistochemical Expression of DNA Mismatch Repair Proteins in the Prognosis of Gliomas

Document Type : Research Articles

Authors

¹ Department of Pathology, Faculty of Medicine, Zagazig University, Egypt.

² Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Egypt.

³ Department of Neurosurgery, Faculty of Medicine, Zagazig University, Egypt.

⁴ Department of Medical Oncology, Faculty of Medicine, Zagazig University, Egypt.

⁵ Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Zagazig University, Egypt.

⁶ Faculty of Medicine, Zagazig University, Egypt.

⁷ Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Egypt.

⁸ Department of Surgery, Faculty of Medicine, Zagazig University, Egypt.

⁹ Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Egypt.

10.31557/APJCP.2025.26.4.1447

Abstract

Background: Gliomas comprise about a third of all brain tumors and 80% of malignant brain cancers. Isocitrate dehydrogenase (IDH) normally converts isocitrate to α-ketoglutarate (α-KG), but mutant IDH gives an oncometabolite, 2-hydroxyglutarate (2-HG) that inhibits α-KG-dependent dioxygenases and inhibits cellular differentiation. Objectives: This work aims to study the mutation in the IDH1 gene and the expression of mismatch repair (MMR) proteins in gliomas and to study the relationship between IDH1 mutation and MMR expression and the prognosis of gliomas. Methods: This study included 60 patients with gliomas. Brain tissues were used for DNA extraction with subsequent mutation analysis. Paraffin blocks of brain tissues were prepared for routine histopathological examination and immunohistochemical examination of MMR proteins. Results: IDH1 mutation and MLH1 and MSH2 expressions were not statistically associated with any of the studied patient or tumor characteristics. No statistically significant association was observed between MSH6 expression in the studied patients and tumor characteristics. No significant association was detected between IHC expression for MLH1, MSH6, MSH2 expression, and IDH1 mutation. No significant association was determined between the expression of MSH6 and IDH1 mutation, or MLH1 expression. A significant association was determined between MSH2 and MSH6 expression. There was a significant association between IDH1 mutation, MSH6, and MSH2 expressions and glioma progression-free survival (PFS). Log Rank test showed that mutant IDH1 and MSH6 expressions had a favorable prognosis. Conclusion: IDH1 mutation and MMR proteins (MLH1, MSH6, and MSH2) could help predict glioma outcome.

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