Abstract
Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. The latter is mutually exclusive to ATRX immunohistochemical loss and has been recently associated with the loss of H3K27me3 immunostaining. We aimed to assess the diagnostic and prognostic value of H3K27me3 immuno-expression in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology. H3K27me3 immunostaining was performed in 69 diffuse gliomas with oligodendroglial (n = 62) or oligoastrocytic (n = 7) morphology. The integration with routinely assessed IDH mutations, ATRX immunostaining, and 1p/19q codeletion classified these cases as 60 oligodendroglial and 9 astrocytic. H3K27me3 was lost in 58/60 oligodendrogliomas with retained (n = 47) or non-conclusive (n = 11) ATRX staining, 3/6 IDH-mutant astrocytomas with ATRX loss, and 3/3 IDH-wt astrocytomas. H3K27me3 was retained in 2/60 oligodendrogliomas with retained ATRX, and in 3/6 IDH-mutant astrocytomas, two of which had lost and one retained ATRX. The combination of H3K27me3 and ATRX immunostainings with IDH mutational status correctly classified 55/69 (80%) cases. In IDH-mutant gliomas, ATRX loss indicates astrocytic phenotype, while ATRX retention and H3K27me3 loss identify oligodendroglial phenotype. Only 14 (20%) IDH-mutant cases with retained ATRX and H3K27me3 or inconclusive ATRX immunostaining would have requested 1p/19q codeletion testing to be classified. Furthermore, H3K27me3 retention was associated with significantly shorter relapse-free survival (P < 0.0001), independently from IDH mutation or 1p/19q codeletion (P < 0.005). Our data suggest that adding H3K27me3 immunostaining to the diagnostic workflow of diffuse gliomas with oligodendroglial or mixed morphology is useful for drastically reducing the number of cases requiring 1p/19q codeletion testing and providing relevant prognostic information.
Highlights
The 2016 World Health Organization (WHO) classification of gliomas, by integrating histopathological features with molecular alterations, classifies astrocytic tumours based on the mutational status of IDH1/2 and H3K27M genes, while oligodendrogliomas are defined by the co-occurrence of IDH1/IDH2 mutation and codeletion of whole chromosomal arms 1p and 19q [1]
We reviewed all cases operated between January 2014 and March 2020 at the University Hospital of Verona, Italy, and morphologically classified oligodendroglioma (OD), anaplastic oligodendroglioma (AOD), oligoastrocytoma (OAS), anaplastic oligoastrocytoma (AOAS), or glioblastoma with oligodendroglial component (GBM-O)
The diagnosis of oligodendroglioma requires the coexistence of IDH1/2 mutation and 1p/19q codeletion [1]
Summary
The 2016 World Health Organization (WHO) classification of gliomas, by integrating histopathological features with molecular alterations, classifies astrocytic tumours based on the mutational status of IDH1/2 and H3K27M genes, while oligodendrogliomas are defined by the co-occurrence of IDH1/IDH2 mutation and codeletion of whole chromosomal arms 1p and 19q [1]. It is unable to discriminate between complete and partial deletions of 1p and 19q because commercial probes hybridize to a minimal part of the chromosome arms, at 1p36 and 19q13 loci [8, 9] It cannot establish with certainty 1p/19q codeletion in the context of imbalanced aneuploidy, polyploidy, or polysomy [7, 9]. The identification of surrogate markers of 1p/19q codeletion based on immunostaining may facilitate the differential diagnosis between astrocytoma and oligodendroglioma in routine practice
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