title: Molecular classification defines 4 prognostically distinct glioma groups irrespective of diagnosis and grade.
abstract: 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 α 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.
authors: From the Molecular Pathology Research Unit (PM, MM, THI, BM) and Departments of Pathology (MM) and Neurosurgery (ARDL), Virgen de la Salud Hospital, Toledo; Department of Biochemistry and Genetics, University of Navarra School of Sciences, Pamplona (JSC); Department of Pathology, MD Anderson International, Madrid (JFG); Department of Pathology, University Hospital Complex of Vigo, Vigo (CF); Department of Pathology, University Clinic Hospital, Barcelona (TR); and IdiPaz Research Unit, La Paz University Hospital, Madrid (JAR), Spain.
authors: Pilar
authors: P
authors: Mur
authors: Manuela
authors: M
authors: Mollejo
authors: Teresa
authors: T
authors: Hernández-Iglesias
authors: Ángel Rodríguez
authors: ÁR
authors: de Lope
authors: Javier S
authors: JS
authors: Castresana
authors: Juan F
authors: JF
authors: García
authors: Concepción
authors: C
authors: Fiaño
authors: Teresa
authors: T
authors: Ribalta
authors: Juan A
authors: JA
authors: Rey
authors: Barbara
authors: B
authors: Meléndez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005910:Glioma / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000145:classification / Q000379:methods; D014015:Tissue Banks; D055815:Young Adult