ATRX immunohistochemistry can help refine ‘not elsewhere classified’ categorisation for grade II/III gliomas

Abstract

Purpose: The 2016 WHO tumour classification highlights the role of IDH1/2 gene mutation and 1p/19q co-deletion in classifying grade II/III gliomas. A recent cIMPACT-NOW update proposes the use of the term ‘Not Elsewhere Classified’ (NEC) for IDH-mutant, non co-deleted tumours. Here we show how the incorporation of ATRX immunohistochemistry can be used to better delineate the NEC group.

Methods: Clinical data was collected for 112 patients (59% male) treated at our unit. Mutations in IDH1/2 genes were detected by pyrosequencing or immunohistochemistry, 1p/19q co-deletion was assessed with fluorescence in situ hybridisation and ATRX status was determined using immunohistochemical techniques. Tumours were grouped on the basis of molecular markers and outcomes compared.

Results: The mean age of diagnosis was 42.6 years (20–73 years). There were 88 oligodendrogliomas (II = 47, III = 41), 18 diffuse astrocytomas (II = 9, III = 9) and 6 oligoastrocytomas (II = 4, III = 2). The majority of gliomas (87.5%) had mutations in IDH1/2. 1p/19q co-deletion was significantly associated with oligodendroglial morphology (p = < 0.001) and was mutually exclusive with ATRX mutation. Classification on the basis of molecular information showed a significant different in survival between the groups.

Conclusions: ATRX immunohistochemisty is a useful adjunct which can be used with IDH mutation status, 1p/19q co-deletion and histological findings to further define tumour groups. More work is needed to understand the molecular profiles and prognostic implications for non co-deletion, ATRX preserved cases.

Keywords:

• ATRX
• 1p/19q co-deletion
• grade II/III glioma

Acknowledgements

We would like to thank the rest of the neuropathology staff working at King’s College Hospital who helped with the preparation of tissue for analysis.

Disclosure statement

The authors have no conflicts of interest, either financial or personal, to declare.

Authorship

All authors contributed significantly to the collection, processing or analysis of samples. CB and RL were responsible for drafting the initial manuscript with input from all authors. KA and SAS reviewed the final manuscript.