Stains & CD markers
IDH1 (R132H)


Last author update: 12 May 2022
Last staff update: 12 May 2022

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PubMed Search: IDH1

Chunyu Cai, M.D., Ph.D.
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Cite this page: Cai C. IDH1 (R132H). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsidh1.html. Accessed December 3rd, 2022.
Definition / general
  • Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to produce α ketoglutarate (also known as 2 oxoglutarate [2OG]), NAPDH and CO2 (Genes Dev 2013;27:836)
Essential features
  • IDH mutations were first identified in a small percent of glioblastomas and later found in the majority of adult low grade diffuse gliomas (Science 2008;321:1807, N Engl J Med 2009;360:765)
  • IDH mutant gliomas have a better prognosis than the IDH wild type counterparts
  • Over 90% of IDH mutations in gliomas are a missense mutation of IDH1 amino acid 132 (from arginine [R] to histidine [H]), which can be detected by mutation specific immunostain IDH1 R132H (Acta Neuropathol 2009;118:599, Neuropathology 2020;40:68)
  • IDH mutations have also been identified in some nonglioma tumor types (outlined in Positive staining - disease); however, those tumors are dominated by non IDH1 R132H mutations and thus have very little utility for the IDH1 R132H immunostain
Pathophysiology
  • Mutant IDH enzymes produce (R)-2-hydroxyglutarate ([R]-2HG) instead of 2OG, which results in widespread DNA hypermethylation and a unique glioma CpG island methylator phenotype (G CIMP) in IDH mutant gliomas (Nature 2012;483:479)
  • Abnormal accumulation of tumor metabolite 2HG allows detection of IDH mutant glioma in live patients by magnetic resonance spectroscopy (MRS) (Neuro Oncol 2016;18:1559)
Diagrams / tables

Images hosted on other servers:
Role in TCA cycle

Role in TCA cycle

Catalyzation of wild type and mutant IDH1 and IDH2 reactions

Catalyzation of wild type and mutant IDH1 and IDH2 reactions

Uses by pathologists
  • IDH1 R132H immunostain is widely used in pathology laboratories on brain tumors in order to classify diffuse gliomas and provide prognostic implications
  • Multispecific mutant IDH1 / IDH2 immunostain (clone MsMab1) that detects mutant IDH1 (R132H, R132S, R132G) and IDH2 (R172S, R172G) or monoclonal antibody (clone 11C8B1) that detects mutant IDH2 R172T
  • Multiple monoclonal antibodies that target other individual IDH1 / IDH2 mutations and another multispecific mAbs (i.e., MsMab2) that recognizes IDH1 R132L and IDH2 R172M are available but have not gained significant clinical utility in pathology laboratories (Brain Tumor Pathol 2015;32:3)
Prognostic factors
  • Diffuse glioma: IDH mutant gliomas have better prognosis than their IDH wild type counterparts (N Engl J Med 2009;360:765)
  • Acute myeloid leukemia (AML): IDH1 mutations are associated with worse overall survival (hazard ratio: 1.17; 95% CI: 1.02 - 1.36) and a lower complete remission rate (risk ratio: 1.30; 95% CI: 1.04 - 1.63) (Am J Blood Res 2012;2:254)
  • Chondrosarcoma: IDH1 / IDH2 mutations are associated with worse overall survival (hazard ratio: 1.90; 95% CI: 1.06 - 3.42; p: 0.03) (Cancer Med 2021;10:4415)
Microscopic (histologic) description
  • IDH1 (R132H) mutant gliomas show diffuse cytoplasmic reactivity in all tumor cells on IDH1 R132H immunostains
Microscopic (histologic) images

Contributed by Chunyu Cai, M.D., Ph.D. and Justin Bishop, M.D.
IDH low grade astrocytoma

IDH low grade astrocytoma

IDH high grade astrocytoma

IDH high grade astrocytoma

IDH oligodendroglioma

IDH oligodendroglioma

IDH1 / IDH2 MsMab1 IHC on SNUC

IDH1 / IDH2 MsMab1 IHC on SNUC



Contributed by GenomeMe
Astrocytoma: IDH1 R132H, clone IHC132

Astrocytoma: IDH1 R132H, clone IHC132

Glioma: IDH1 R132H, clone IHC132 Glioma: IDH1 R132H, clone IHC132

Glioma: IDH1 R132H, clone IHC132

Positive staining - normal
  • IDH1 R132H is a mutation specific monoclonal antibody and is negative in normal tissue
Positive staining - disease
  • Glial neoplasms:
    • By definition, all oligodendrogliomas harbor IDH1 / IDH2 mutation
    • Vast majority of adult type diffuse astrocytomas are IDH mutant
  • Nonglial neoplasms:
Negative staining
  • CNS neoplasms:
    • Within the CNS, IDH R132H is considered a specific marker for a subset of adult diffuse gliomas and is not expressed in pediatric type diffuse gliomas, circumscribed gliomas, glioneuronal tumors, ependymal tumors, choroid plexus tumors or mesenchymal tumors (N Engl J Med 2009;360:765)
    • Of diffuse gliomas, IDH R132H mutation is not found in wild type glioblastoma, H3F3A G34R or K27M mutant gliomas; IDH mutation is uncommon in infratentorial, spinal cord diffuse gliomas and pediatric gliomas under 14 years of age (Acta Neuropathol Commun 2016;4:60, Acta Neuropathol 2012;124:449, Childs Nerv Syst 2011;27:87)
  • Non CNS neoplasms:
    • IDH1 R132H immunostain is negative in 258 thyroid, 11 renal cell, 10 ovarian, 18 endometrial, 20 breast, 25 colorectal, 22 non small cell lung carcinomas, 25 melanomas and 8 thyroid follicular adenomas (Appl Immunohistochem Mol Morphol 2014;22:284)
    • In the initial study, IDH1 / IDH2 mutation was not detected in 494 non CNS tumors, including 35 lung cancers, 57 gastric cancers, 27 ovarian cancers, 96 breast cancers, 114 colorectal cancers, 95 pancreatic cancers, 7 prostate cancers, 4 chronic myelogenous leukemias, 7 chronic lymphocytic leukemias, 7 acute lymphoblastic leukemias and 45 acute myelogenous leukemias (N Engl J Med 2009;360:765)
Sample pathology report
  • Brain, left frontal lobe mass, excision:
    • Astrocytoma, IDH mutant, WHO grade 2
Board review style question #1

Which of the following is the most common IDH mutation in diffuse gliomas?

  1. IDH1 R132G
  2. IDH1 R132H
  3. IDH1 R132L
  4. IDH2 R172K
  5. IDH2 R172S
Board review style answer #1
B. IDH1 R132H

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Reference: IDH1 (R132H)
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