Isocitrate dehydrogenase 1 (IDH1) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, producing NADPH (1). However, abnormal IDH1 caused by somatic missense mutations may occur when substitution from arginine to histidine at codon 132 (IDH1 R132H) inhibits the wild-type IDH1 enzymatic activity, leading to production of 2-hydroxyglutarate, a possible oncometabolite. The accumulated oncometabolite promotes formation and malignant progression of gliomas (2). IDH1 R132H detection by immunohistochemistry can be used for the diagnostic differentiation between grade II/III gliomas, secondary glioblastomas and primary glioblastomas. The IDH1 R132H mutation correlates with a positive clinical outcome in patients with astrocytic tumors. Recently, studies indicated that IDH mutations along with ATRX status, and in combination with other classical biomarkers, helped refine the molecular classification of adult gliomas, providing a prognostic tool for clinicians (3). Data indicate that IDH1 R132H expression could be used as a predictive marker of prognosis for patients with gastrointestinal cancer (1).
1. Li J, Huang, et al. Decreased expression of IDH1-R132H correlates with poor survival in gastrointestinal cancer. Oncotarget 2016 Nov; 8;7(45): 73638-50.
2. Newton H. Handbook of Brain Tumor Chemotherapy, Molecular Therapeutics and Immunotherapy (Second Edition). 2018: 557-68.
3. Cai J, et al. ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors. Oncoscience. 2016 Sep; 3(7-8):258-65.
4. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
5. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.