Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 74, Issue 3, Pages 241-249Publisher
OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0000000000000167
Keywords
1p/19q codeletion; ATRX alteration; Glioma; IDH mutation
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Funding
- Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion [PI10/01974, PI10/01972, CA12/00318, PI13/00800, INT13/046, PT13/0010/0007, PI13/00055]
- Fondo Europeo de Desarrollo Regional (FEDER) Union Europea Una manera de hacer Europa
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According to World Health Organization criteria, diffuse gliomas are divided into several histological subtypes, including astrocytomas, oligodendrogliomas, and oligoastrocytomas, and 4 malignancy grades (I-IV). Molecular alterations, such as the isocitrate dehydrogenase gene (IDH) mutation or 1p/19q loss, are found in these tumors but are not included in the current classification system. Recently, mutation of alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene and its loss of expression have been reported in infiltrating gliomas. We evaluated ATRX protein expression in 272 gliomas and its association with molecular and clinical features. Loss of ATRX expression was more common in tumors with an astrocytic component (astrocytomas II/III, 46.4%; oligoastrocytomas, 47.5%) but was uncommon in oligodendrogliomas (7.3%) and glioblastomas (0.9%). In astrocytic tumors, loss of ATRX expression was significantly associated with longer overall survival. Remarkably, on the basis of IDH mutation, 1p/19q codeletion, and ATRX expression, our study defined 4 molecularly and prognostically different groups of gliomas, showing the relevance of ATRX expression as a new marker for refining the molecular classification of gliomas and for distinguishing clinically distinct prognostic subgroups of patients.
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