Difference between revisions of "IDH-1"

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==Tumours==
==Tumours==
*[[Oligodendroglioma]]<ref>{{Cite journal  | last1 = Capper | first1 = D. | last2 = Reuss | first2 = D. | last3 = Schittenhelm | first3 = J. | last4 = Hartmann | first4 = C. | last5 = Bremer | first5 = J. | last6 = Sahm | first6 = F. | last7 = Harter | first7 = PN. | last8 = Jeibmann | first8 = A. | last9 = von Deimling | first9 = A. | title = Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. | journal = Acta Neuropathol | volume = 121 | issue = 2 | pages = 241-52 | month = Feb | year = 2011 | doi = 10.1007/s00401-010-0770-2 | PMID = 21069360 }}</ref>
*[[Oligodendroglioma]] <ref>{{Cite journal  | last1 = Capper | first1 = D. | last2 = Reuss | first2 = D. | last3 = Schittenhelm | first3 = J. | last4 = Hartmann | first4 = C. | last5 = Bremer | first5 = J. | last6 = Sahm | first6 = F. | last7 = Harter | first7 = PN. | last8 = Jeibmann | first8 = A. | last9 = von Deimling | first9 = A. | title = Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. | journal = Acta Neuropathol | volume = 121 | issue = 2 | pages = 241-52 | month = Feb | year = 2011 | doi = 10.1007/s00401-010-0770-2 | PMID = 21069360 }}</ref>
*[[Astrocytoma]]
*[[Astrocytoma]]
*Secondary [[glioblastoma]]
*Secondary [[glioblastoma]]
*[[Myelodysplasia]]<ref>{{Cite journal  | last1 = Andrulis | first1 = M. | last2 = Capper | first2 = D. | last3 = Luft | first3 = T. | last4 = Hartmann | first4 = C. | last5 = Zentgraf | first5 = H. | last6 = von Deimling | first6 = A. | title = Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing. | journal = Leuk Res | volume = 34 | issue = 8 | pages = 1091-3 | month = Aug | year = 2010 | doi = 10.1016/j.leukres.2010.02.014 | PMID = 20227112 }}</ref>
*[[Myelodysplasia]] <ref>{{Cite journal  | last1 = Andrulis | first1 = M. | last2 = Capper | first2 = D. | last3 = Luft | first3 = T. | last4 = Hartmann | first4 = C. | last5 = Zentgraf | first5 = H. | last6 = von Deimling | first6 = A. | title = Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing. | journal = Leuk Res | volume = 34 | issue = 8 | pages = 1091-3 | month = Aug | year = 2010 | doi = 10.1016/j.leukres.2010.02.014 | PMID = 20227112 }}</ref>
*[[Acute myeloid leukemia]]
*[[Acute myeloid leukemia]]
*[[Chondrosarcoma]] <ref>{{Cite journal  | last1 = Amary | first1 = MF. | last2 = Bacsi | first2 = K. | last3 = Maggiani | first3 = F. | last4 = Damato | first4 = S. | last5 = Halai | first5 = D. | last6 = Berisha | first6 = F. | last7 = Pollock | first7 = R. | last8 = O'Donnell | first8 = P. | last9 = Grigoriadis | first9 = A. | title = IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. | journal = J Pathol | volume = 224 | issue = 3 | pages = 334-43 | month = Jul | year = 2011 | doi = 10.1002/path.2913 | PMID = 21598255 }}</ref>


===Negative===
===Negative===
Line 32: Line 33:
*[[Pilocytic astrocytoma]]
*[[Pilocytic astrocytoma]]
*Neuronal tumors
*Neuronal tumors
*Sarcoma, carcinoma <ref>{{Cite journal  | last1 = Sahm | first1 = F. | last2 = Capper | first2 = D. | last3 = Meyer | first3 = J. | last4 = Hartmann | first4 = C. | last5 = Herpel | first5 = E. | last6 = Andrulis | first6 = M. | last7 = Mechtersheimer | first7 = G. | last8 = Petersen | first8 = I. | last9 = Paulus | first9 = W. | title = Immunohistochemical analysis of 1844 human epithelial and haematopoietic tumours and sarcomas for IDH1R132H mutation. | journal = Histopathology | volume = 58 | issue = 7 | pages = 1167-72 | month = Jun | year = 2011 | doi = 10.1111/j.1365-2559.2011.03823.x | PMID = 21707716 }}</ref>
*Sarcoma, carcinoma <ref>{{Cite journal  | last1 = Sahm | first1 = F. | last2 = Capper | first2 = D. | last3 = Meyer | first3 = J. | last4 = Hartmann | first4 = C. | last5 = Herpel | first5 = E. | last6 = Andrulis | first6 = M. | last7 = Mechtersheimer | first7 = G. | last8 = Petersen | first8 = I. | last9 = Paulus | first9 = W. | title = Immunohistochemical analysis of 1844 human epithelial and haematopoietic tumours and sarcomas for IDH1R132H mutation. | journal = Histopathology | volume = 58 | issue = 7 | pages = 1167-72 | month = Jun | year = 2011 | doi = 10.1111/j.1365-2559.2011.03823.x | PMID = 21707716 }}</ref> - note that some Cholangiocarcinoma contain IDH1 R132C or R172K mutations.<ref>{{Cite journal  | last1 = Farshidfar | first1 = F. | last2 = Zheng | first2 = S. | last3 = Gingras | first3 = MC. | last4 = Newton | first4 = Y. | last5 = Shih | first5 = J. | last6 = Robertson | first6 = AG. | last7 = Hinoue | first7 = T. | last8 = Hoadley | first8 = KA. | last9 = Gibb | first9 = EA. | title = Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles. | journal = Cell Rep | volume = 18 | issue = 11 | pages = 2780-2794 | month = Mar | year = 2017 | doi = 10.1016/j.celrep.2017.02.033 | PMID = 28297679 }} not detected by IHC.</ref>
 
==Functional meaning==
The R132H amino acic exchange alters the enzymatic activity of IDH resulting in production D-2-hydroxyglutarate (D-2HG).<ref>{{Cite journal  | last1 = Longuespée | first1 = R. | last2 = Wefers | first2 = AK. | last3 = De Vita | first3 = E. | last4 = Miller | first4 = AK. | last5 = Reuss | first5 = DE. | last6 = Wick | first6 = W. | last7 = Herold-Mende | first7 = C. | last8 = Kriegsmann | first8 = M. | last9 = Schirmacher | first9 = P. | title = Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry. | journal = Acta Neuropathol Commun | volume = 6 | issue = 1 | pages = 21 | month = 03 | year = 2018 | doi = 10.1186/s40478-018-0523-3 | PMID = 29499756 }}</ref> Therefore the mutated enzyme  is considered an oncometabolite.
[[File:Wild-type_and_mutant_IDH1_structures.png|400px]]




Latest revision as of 14:13, 14 March 2018

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.

  • IDH-1 (R132H) in a secondary glioblastoma

  • IDH-1 in a oliogoastrocytoma grade II

  • Absence of IDH-1 in a primary glioblastoma

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.
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