Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas

AIMS: We performed an immunohistochemical analysis of alpha-thalassaemia/mental retardation syndrome X-linked (ATRX) expression in adult diffuse gliomas, with reference to clinicopathological and genetic features, to determine the utility of this analysis in diagnostic practice. METHODS AND RESULTS: A total of 193 adult diffuse gliomas underwent immunohistochemical analysis. In areas in which internal controls, neurones, glia and blood vessels were properly stained, the ATRX immunoreactivity of tumour cells was either almost totally absent or completely retained in all cases. There was perfect concordance between the immunohistochemical results and ATRX mutation status, which was known in 19 cases. ATRX loss was observed in 54.5, 30.8 and 0.0% of grades II/III astrocytomas, oligoastrocytomas and oligodendrogliomas, respectively, and 12.7% of glioblastomas. In grades II/III gliomas, most ATRX-loss cases (92.3%) had IDH1/2 mutations. ATRX loss was associated significantly with TP53 mutation and p53 overexpression (P < 0.001), but was never accompanied by 1p/19q co-deletion. IDH1/2 mutation in ATRX-loss tumours was less frequent in glioblastomas than in grades II/III gliomas (P < 0.001). Further, there was no significant association between ATRX loss and p53 overexpression in glioblastomas. ATRX-loss glioblastomas affected younger patients (P < 0.001) and occurred more frequently in locations other than the cerebral hemispheres (P = 0.006). Most grades II/III gliomas (93.3%) were categorized into three molecular subtypes based on the status of IDH1/2 mutation, ATRX immunohistochemistry and 1p/19q co-deletion. CONCLUSIONS: Distinct histological and molecular characteristics of adult diffuse gliomas with and without ATRX immunoreactivity indicate the utility of ATRX immunohistochemistry in diagnostic practice.