Lack of H3K27 trimethylation is associated with 1p/19q codeletion in diffuse gliomas

Nuclear H3 K27me3 is retained in both components of dual genotype oligoastrocytoma

“…However, careful assessment of tumor morphology and of immunoreactivity for ATRX and p53, as indicated by the C-IMPACT-NOW Working Committee 3, 3 allowed the identification of two morphologically and genetically different tumor components and a final diagnosis of dual genotype oligoastrocytoma (Fig 3). Although patients with tumors retaining H3 K27me3 had significantly worse survival in the study by Filipski et al, 5 further studies are warranted to verify whether the prognostic value of this marker in diffuse gliomas is independent from IDH mutational status, histological grade, or tumor histotype. Indeed, this patient with dual genotype oligoastrocytoma, who underwent gross total resection and had no adjuvant therapies, is alive, with no tumor recurrence after 43 months of follow up.…”

“…Based on these findings, we confirm that retention of H3 K27me3 is not specific of astrocytic differentiation in diffuse gliomas. In this case, the diagnostic algorithm proposed by Filpski et al, 5 and starting with H3 K27me3 immunohistochemistry, would have led to a diagnosis of astrocytoma, because of the retained H3 K27me3 nuclear expression (Fig 3). However, careful assessment of tumor morphology and of immunoreactivity for ATRX and p53, as indicated by the C-IMPACT-NOW Working Committee 3, 3 allowed the identification of two morphologically and genetically different tumor components and a final diagnosis of dual genotype oligoastrocytoma (Fig 3).…”

“…3 However, a recent study proposed a novel diagnostic tree, starting with the assessment of H3 K27me3 (trimethylation of lysine residue at codon 27 of histone 3 protein) staining, for diffuse gliomas. 5 This was based on the observation that in a cohort of 161 diffuse gliomas, 96% oligodendrogliomas lacked nuclear expression of H3 K27me3, and the retained nuclear expression of H3 K27me3 was diagnostic of astrocytoma, with a predicted probability score of 0.9995. 5 According to the suggested algorithm, tumors with nuclear retention of H3 K27me3 should be diagnosed as having astrocytomas with no further testing, while tumors lacking nuclear H3 K27me3 should be analyzed for ATRX staining.…”

“…5 This was based on the observation that in a cohort of 161 diffuse gliomas, 96% oligodendrogliomas lacked nuclear expression of H3 K27me3, and the retained nuclear expression of H3 K27me3 was diagnostic of astrocytoma, with a predicted probability score of 0.9995. 5 According to the suggested algorithm, tumors with nuclear retention of H3 K27me3 should be diagnosed as having astrocytomas with no further testing, while tumors lacking nuclear H3 K27me3 should be analyzed for ATRX staining. Then, if ATRX expression is lost, the diagnosis of astrocytoma can be rendered with no further testing; if it is retained, IDH1 R132H staining should be assessed, indicating oligodendroglioma if positive and astrocytoma if negative.…”

“…Then, if ATRX expression is lost, the diagnosis of astrocytoma can be rendered with no further testing; if it is retained, IDH1 R132H staining should be assessed, indicating oligodendroglioma if positive and astrocytoma if negative. 5 Findings of a subsequent study by another group advised against this diagnostic approach. 6 Indeed, in a cohort of 102 diffuse gliomas, 25% of oligodendrogliomas showed retention of nuclear H3 K27me3 and they would have been misclassified as astrocytomas using an algorithm starting with H3 K27me3 immunohistochemistry.…”