• All IHC stains will include a positive control tissue

• This antibody can detect individual infiltrating glioma cells which have this mutation, within the background of normal brain, reactive astrogliosis, treatment effects, etc.
• Given the superb specificity of melting curve analysis and DNA sequencing, these molecular tests are preferred when sufficient viable-appearing neoplasm is available. However, molecular study is limited by neoplastic DNA quantity, which can be greatly diluted by background brain tissue, reactive astrogliosis, inflammation, etc. Hence, immunohistochemistry for the R132H mutation is most appropriate in very scant or dilute samples, where individual infiltrating glioma cells may be visualized. A positive stain provides direct evidence of both neoplasia and of infiltration
• In some cases, nonspecific background staining or regional heterogeneity of IDH1-R132H protein expression has been reported (see reference 7 below, for example) and may necessitate confirmatory genetic analysis.

• Unlabeled/mislabeled block
• Insufficient tissue
• Slides broken beyond repair

Submit a formalin-fixed, paraffin-embedded tissue

Formalin-fixed, paraffin-embedded (FFPE) tissue block

FFPE tissue section mounted on a charged, unstained slide

Ambient (preferred)

Immunohistochemical staining and microscopic examination

If requested, an interpretive report will be provided

Specifications

• Antibody that recognizes the most common mutant of IDH1 R132H-a change in codon 132 of the IDH1 gene that replaces arginine with histidine, causing a sufficient conformational shift within the protein to be detected by immunohistochemistry
• Approximately 70% of infiltrating grade II and grade III gliomas contain this particular mutation
• Other IDH1 and IDH2 mutations are NOT detected by the antibody

Staining pattern

• Cytoplasmic staining

References

1. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009 Feb 19;360(8):765-773.
2. Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 2010 Feb 15;207(2):339-344.
3. Capper D, Weissert S, Balss J, Habel A, Meyer J, Jager D, et al. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 2010 Jan;20(1):245-254.
4. Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A. Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 2009 Nov;118(5):599-601.
5. Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J. Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol 2010 Aug;34(8):1199-1204.
6. Horbinski C, Kofler J, Yeaney G, Camelo-Piragua S, Venneti S, Louis DN, et al. Isocitrate dehydrogenase 1 analysis differentiates gangliogliomas from infiltrative gliomas. Brain Pathol 2011 Sep;21(5):564-574.
7. Preusser M, Wohrer A, Stary S, Hoftberger R, Streubel B, Hainfellner JA. Value and limitations of immunohistochemistry and gene sequencing for detection of the IDH1-R132H mutation in diffuse glioma biopsy specimens. J Neuropathol Exp Neurol 2011 Aug;70(8):715-723.

Medical necessity