IDH-1

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IDH1 staining in oligodendroglioma.

Isocitrate dehydrogenase 1 (R132H), often abbreviated IDH1 or IDH-1 is a mutation-specific antibody detecting the R132H mutation in tumor material.[1]

Positive staining

  • Cytoplasmic[2]
    • Does not stain endothelial cells and inflammatory cells.

Note:

  • The antibody does not detect other rare IDH-1/2 mutations (ie. R132G or R172K).

Normal tissues

  • Absent

Tumours

Negative

Negative staining:[6]

  • Non-tumorous tissue, endothelial cells.
  • Ependymoma
  • Pilocytic astrocytoma
  • Neuronal tumors
  • Sarcoma, carcinoma [7] - note that some Cholangiocarcinoma contain IDH1 R132C or R172K mutations.[8]

Functional meaning

The R132H amino acic exchange alters the enzymatic activity of IDH resulting in production D-2-hydroxyglutarate (D-2HG).[9] Therefore the mutated enzyme is considered an oncometabolite. Wild-type and mutant IDH1 structures.png


See also

References

  1. Capper, D.; Zentgraf, H.; Balss, J.; Hartmann, C.; von Deimling, A. (Nov 2009). "Monoclonal antibody specific for IDH1 R132H mutation.". Acta Neuropathol 118 (5): 599-601. doi:10.1007/s00401-009-0595-z. PMID 19798509.
  2. Capper, D.; Weissert, S.; Balss, J.; Habel, A.; Meyer, J.; Jäger, D.; Ackermann, U.; Tessmer, C. et al. (Jan 2010). "Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors.". Brain Pathol 20 (1): 245-54. doi:10.1111/j.1750-3639.2009.00352.x. PMID 19903171.
  3. Capper, D.; Reuss, D.; Schittenhelm, J.; Hartmann, C.; Bremer, J.; Sahm, F.; Harter, PN.; Jeibmann, A. et al. (Feb 2011). "Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology.". Acta Neuropathol 121 (2): 241-52. doi:10.1007/s00401-010-0770-2. PMID 21069360.
  4. Andrulis, M.; Capper, D.; Luft, T.; Hartmann, C.; Zentgraf, H.; von Deimling, A. (Aug 2010). "Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing.". Leuk Res 34 (8): 1091-3. doi:10.1016/j.leukres.2010.02.014. PMID 20227112.
  5. Amary, MF.; Bacsi, K.; Maggiani, F.; Damato, S.; Halai, D.; Berisha, F.; Pollock, R.; O'Donnell, P. et al. (Jul 2011). "IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours.". J Pathol 224 (3): 334-43. doi:10.1002/path.2913. PMID 21598255.
  6. Capper, D.; Reuss, D.; Schittenhelm, J.; Hartmann, C.; Bremer, J.; Sahm, F.; Harter, PN.; Jeibmann, A. et al. (Feb 2011). "Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology.". Acta Neuropathol 121 (2): 241-52. doi:10.1007/s00401-010-0770-2. PMID 21069360.
  7. Sahm, F.; Capper, D.; Meyer, J.; Hartmann, C.; Herpel, E.; Andrulis, M.; Mechtersheimer, G.; Petersen, I. et al. (Jun 2011). "Immunohistochemical analysis of 1844 human epithelial and haematopoietic tumours and sarcomas for IDH1R132H mutation.". Histopathology 58 (7): 1167-72. doi:10.1111/j.1365-2559.2011.03823.x. PMID 21707716.
  8. Farshidfar, F.; Zheng, S.; Gingras, MC.; Newton, Y.; Shih, J.; Robertson, AG.; Hinoue, T.; Hoadley, KA. et al. (Mar 2017). "Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.". Cell Rep 18 (11): 2780-2794. doi:10.1016/j.celrep.2017.02.033. PMID 28297679. not detected by IHC.
  9. Longuespée, R.; Wefers, AK.; De Vita, E.; Miller, AK.; Reuss, DE.; Wick, W.; Herold-Mende, C.; Kriegsmann, M. et al. (03 2018). "Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry.". Acta Neuropathol Commun 6 (1): 21. doi:10.1186/s40478-018-0523-3. PMID 29499756.