Classification of diffuse Gliomas

Glioma Diagnosis by IHC

The routine practical approach for diagnosing astrocytomas and oligodendrogliomas begins with perfoming IHC for ATRX and IDH1 R132H expression. Stepwise analysis of molecular parameters with initial IHC for ATRX and IDH1 R132H followed by 1p/19q analysis and then by IDH sequencing significantly reduces the number of molecular tests required for unequivocal diagnosis (Reus et al., 2015).

Characteristics of the 3 most important molecular groups of adult glioma:

Diffuse glioma with IDH mutation & 1p/19q-codeletion Diffuse glioma with IDH mutation Diffuse glioma without IDH mutation
Biomarker
IDH1/2 mutated mutated wildtype
1p/19q co-deleted intact intact
ATRX nuclear expression loss of nuclear expression nuclear expression
hTERT-Promotor mutated wildtype mutated
Typical histological finding and prognosis
Histology
Oligodendroglial Astrocytic Astrocytic
WHO grading
II or III
II or III (IV)
IV (II or III)
Median survival
more than 15 years
8-12 years
less than 2-3 years

Combined IHC on IDH1 R132H (clone H09) and ATRX (clone AX1) substitutes molecular testing.

Anti-IDH1 R132H
clone H09
#DIA-H09
0.5ml
1:20-1:50

IDH1 R132H
The 2016 CNS WHO certification recommends IDH1 R132H IHC as a backbone for differential diagnosis of glioma. IDH1 R132H IHC is widely applied as a favorable prognostic marker.

Anti-ATRX
clone AX1
#DIA-AX1
0.5ml
1:100-1:200

ATRX
ATRX mutations in gliomas result in the loss of nuclear ATRX expression (right), which can be diagnosed by IHC analysis. Loss of ATRX expression is close to being mutually exclusive to 1p/19q co-deletion.

p53 and Ki67 are helpful accessory marker for classification of diffuse glioma.

Anti-p53
clone CC53
#DIA-530
0.5ml
1:100-1:200

p53
p53 can be selected as a marker since there is evidence of relationships among p53, mutually exclusive to 1p/19q deletion, suggesting the usesfulness of ATRX and p53 IHC without 1p/19q analysis.

Anti-Ki67
clone Ki67P
#DIA-670
0.5ml
1:100-1:200

Ki-67
High Ki-67 is dominant in IDH wild type gliomas and low Ki-67 is associaterd with IDH1 mutation in primary glioblastomas. The mitotic index is significantly associated with outcome of IDH wild type tumors.

REFERENCE:

Reuss DE et al. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol. 129(1):133-146, 2015

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