Classification of diffuse gliomas
IHC for ATRX and IDH1 R132H
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 and 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.
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.
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.
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.
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.
Medical devices for in vitro diagnostic. Read the instruction for use carefully.