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
Diffuse glioma with
Diffuse glioma without
loss of nuclear expression
Typical histological finding and prognosis
II or III
II or III (IV)
IV (II or III)
Combined IHC on IDH1 R132H (clone H09) and ATRX (clone AX1) substitutes molecular testing.
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.
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.
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