Mur Pilar, Mollejo Manuela, Hernández-Iglesias Teresa, de Lope Ángel Rodríguez, Castresana Javier S, García Juan F, Fiaño Concepción, Ribalta Teresa, Rey Juan A, Meléndez Barbara
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.
J Neuropathol Exp Neurol. 2015 Mar;74(3):241-9. doi: 10.1097/NEN.0000000000000167.
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.
根据世界卫生组织的标准，弥漫性胶质瘤可分为几种组织学亚型，包括星形细胞瘤、少突胶质细胞瘤和少突星形细胞瘤，以及4个恶性等级（I-IV级）。这些肿瘤中存在分子改变，如异柠檬酸脱氢酶基因（IDH）突变或1p/19q缺失，但目前的分类系统未将其纳入。最近，有报道称在浸润性胶质瘤中存在α地中海贫血/智力发育迟缓综合征X连锁（ATRX）基因的突变及其表达缺失。我们评估了272例胶质瘤中ATRX蛋白的表达及其与分子和临床特征的相关性。ATRX表达缺失在具有星形细胞成分的肿瘤中更为常见（II/III级星形细胞瘤，46.4%；少突星形细胞瘤，47.5%），但在少突胶质细胞瘤（7.3%）和胶质母细胞瘤（0.9%）中不常见。在星形细胞肿瘤中，ATRX表达缺失与较长的总生存期显著相关。值得注意的是，基于IDH突变、1p/19q共缺失和ATRX表达，我们的研究定义了4个分子和预后不同的胶质瘤组，显示了ATRX表达作为细化胶质瘤分子分类和区分临床不同预后亚组患者的新标志物的相关性。
