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

1p/19q

ATRX

hTERT-Promotor

 

 

mutated

co-deleted

nuclear expression

mutated

 

 

mutated

intact

loss of nuclear expression

wildtype

 

 

wildtype

intact

nuclear expression

mutated

Typical histological finding and prognosis

 

Histology

WHO grading

Median Survival

 

 

oligodendroglial

II or III

>15 years

 

 

astrocytic

II or III (IV)

8-12 years

 

 

astrocytic

IV (II or III)

<2-3 years

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

Glioma Diagnosis by IHC

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.

 

Glioma Diagnosis by IHC

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.

Glioma Diagnosis by IHC

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.

Glioma Diagnosis by IHC

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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