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. 2016 Jun 16;4(1):60.
doi: 10.1186/s40478-016-0331-6.

ATRX immunostaining predicts IDH and H3F3A status in gliomas

Azadeh Ebrahimi  1   2 , Marco Skardelly  3   4   5   2 , Irina Bonzheim  6   2 , Ines Ott  1   2 , Helmut Mühleisen  7 , Franziska Eckert  8   2 , Ghazaleh Tabatabai  4   5   9   10   2 , Jens Schittenhelm  11   12
Affiliations

ATRX immunostaining predicts IDH and H3F3A status in gliomas

Azadeh Ebrahimi et al. Acta Neuropathol Commun. .

Abstract

Gliomas are the most frequent intraaxial CNS neoplasms with a heterogeneous molecular background. Recent studies on diffuse gliomas have shown frequent alterations in the genes involved in chromatin remodelling pathways such as α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX). Yet, the reliability of ATRX in predicting isocitrate dehydrogenase (IDH) and H3 histone, family 3A (H3F3A) mutations in gliomas, is unclear. We analysed the ATRX expression status by immunohistochemistry, in a large series of 1064 gliomas and analysed the results in correlation to IDH, H3F3A and loss of heterozygosity (LOH) 1p/19q status in these tumors. We also investigated the prognostic potential of ATRX concerning the clinical outcome of patients with diffuse gliomas. According to our results, loss of nuclear ATRX expression was accompanied with an astrocytic tumor lineage and a younger age of onset. ATRX loss in astrocytomas was also strongly associated with IDH1/2 and H3F3A mutation (p < 0. 0001). Among 196 glial tumors with nuclear ATRX loss, 173 (89 %) had an IDH1 or IDH2 mutation. Among the remaining 23 cases (11 %) with ATRX loss and IDH wild type status, 7 cases had a H3F3A G34R mutation (3 %) and 2 cases had a H3F3A K27M mutation (1 %). ATRX retention in IDH1/2 mutant tumors was strongly associated with LOH 1p/19q and oligodendroglioma histology (p < 0. 0001) VSports手机版. We also confirmed the significant prognostic role of ATRX. Diffuse gliomas with ATRX loss (n = 137, median 1413 days, 95 % CI: 1065-1860 days) revealed a significantly better clinical outcome compared with tumors with ATRX retention (n = 335, median: 609, 95 % CI: 539-760 days, HR = 1. 81, p < 0. 0001). In conclusion, ATRX is a potential marker for prediction of IDH/H3F3A mutations and substratification of diffuse gliomas into survival relevant tumor groups. Such classification is of great importance for further clinical decision making especially concerning the therapeutic options available for diffuse gliomas. .

Keywords: ATRX; Astrocytoma; Glioma; H3F3A; IDH; Oligodendroglioma. V体育安卓版.

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"VSports最新版本" Figures

Fig. 1
Fig. 1
ATRX immunohistochemistry: a loss of immunoreactivity in necrotic/perinecrotic tumor areas, b Ambiguous ATRX status; areas with clear ATRX retention bordering areas with nuclear ATRX loss. c Diffuse astrocytoma grade II with ATRX loss, d Anaplastic Astrocytoma grade III with ATRX loss, e Oligodendroglioma grade II with ATRX retention, f Anaplastic Ependymoma with ATRX retention (f magnification ×200, a, c–e magnification ×100, b magnification ×40)
Fig. 2
Fig. 2
Representative examples of the detected IDH1, IDH2 and H3F3A mutations. a Electropherogramm of IDH1 p.R132H (c.395G > A), b electropherogramm of IDH2 p.R172K (c.515G > A), c electropherogramm of H3F3A p.G34R (c.100G > A). Blue arrow designates the mutation
Fig. 3
Fig. 3
Kaplan-Meier survival plots. a Diffuse gliomas of WHO G7rade II separated by ATRX status (n = 130); median: 2141 days in ATRX loss group vs. 1175 days in ATRX retention group. b Astrocytoma WHO grade II and III grouped (n = 176), tumors harbouring ATRX loss (n = 96) had a significantly better outcome compared to tumors with ATRX retention (n = 80) (median: 1952 vs. 818 days, p < 0.0001) c Astrocytic, oligodendroglial and mixed tumors without 1p/19q codeletion (n = 230) show a significant better outcome when accompanied with ATRX loss than with ATRX retention (median ATRX loss 1769 days vs. ATRX retention 1127 days, p = 0.0046)
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