Diffuse gliomas in patients aged 55 years or over: A suggestion for IDH mutation testing

Abstract

Diffuse gliomas are defined on the isocitrate dehydrogenase (IDH) gene (IDH) mutational mutational status. The most frequent IDH mutation is IDH1 R132H, which is detectable by immunohistochemistry; other IDH mutations are rare (10%). IDH mutant gliomas have better prognosis. Further, IDH wild-type low-grade (II/III) gliomas have clinical behaviors similar to those of glioblastoma (GBM) and it was suggested that they are submitted to similar post-surgical treatment. The incidence of IDH mutant gliomas (2%) and that of GBMs with non-canonical IDH mutations (< 1%) are very low in patients ≥ 55 years. For this reason, it was suggested that immunohistochemistry against IDH1 R132H is sufficient to classify GBM as IDH wild-type in this age group. However, no indication was provided for IDH mutational testing in low-grade diffuse gliomas. To address this issue, 273 diffuse gliomas were tested for IDH1 R132H immunohistochemistry. 2/4 diffuse astrocytomas (DAs), 4/9 anaplastic astrocytomas (AAs), 2/256 GBMs, and 4/4 oligodendrogliomas had positive staining. No other IDH mutations were found in immuno-negative low-grade cases by DNA sequencing. To validate our findings, we considered 311 diffuse gliomas in patients ≥ 55 years in The Cancer Genome Atlas database. Fifty-five out of 311 gliomas had IDH R132H mutations (9/16 DAs; 8/48 AAs; 3/211 GBMs; 35/36 oligodendrogliomas), one DA, and one oligodendroglioma had other IDH mutations. IDH mutant gliomas had significantly higher frequency of O-6-methylguanine-DNA methyltransferase promoter methylation (P = 0.0008) and longer overall survival (P < 0.0001).In conclusion, low-grade gliomas are a minor part of gliomas (117/584) in patients ≥ 55 years, albeit they represent most IDH mutant gliomas in this age group (64/69 cases). IDH non-canonical mutations can be found in immunonegative low-grade gliomas (2/54). In view of its significance for prognosis and therapeutic management, our results suggest that IDH mutational status is assessed in all diffuse gliomas in patients ≥ 55 years by immunohistochemistry, followed by IDH sequencing in low-grade immunonegative cases.

A Nomogram Modeling 11C-MET PET/CT and Clinical Features in Glioma Helps Predict IDH Mutation

“…Furthermore, next-generation sequencing for the IDH genotype was not available for this retrospective study, and some patients with the mutation may have been misidentified. Non-canonical IDH mutations can be found in IDH1 R132H immune-negative LGG ( 34 ). These points would be addressed in future work.…”

H3K27me3 immunostaining is diagnostic and prognostic in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology

“…Thus, ATRX immunostaining has been suggested as an alternative low-cost marker to d i f f e r e n t i a t e I D H -m u t a n t a s t r o c y t o m a s f r o m oligodendrogliomas [2,10,11]. Nonetheless, a proportion of IDH-mutant astrocytic tumours retain ATRX immunostaining [2,[12][13][14], and ATRX immunostaining has also been reported as non-conclusive in 11.5% of cases [14].…”

Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification

“…Otherwise, IDH1 immunonegative in patients aged greater than 55 years is likely to be IDH-wild type with an incidence rate of < 1% and acts like a high-grade glioma. Meanwhile, IDH1/2 DNA sequencing is preferable for detecting non-canonical mutations[ 15 ]. A non-canonical IDH mutation and a loss of ATRX mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation[ 7 ] have been associated with a family history of cancer and astrocytoma of the infratentorial region being identified at 80% of the time in multicentric astrocytoma[ 16 ].…”