Purkait Suvendu, Miller Christopher A, Kumar Anupam, Sharma Vikas, Pathak Pankaj, Jha Prerana, Sharma Mehar Chand, Suri Vaishali, Suri Ashish, Sharma B S, Fulton Robert S, Kale Shashank Sharad, Dahiya Sonika, Sarkar Chitra
Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO.
Brain Pathol. 2017 Mar;27(2):138-145. doi: 10.1111/bpa.12364. Epub 2016 Jun 13.
This study aims (1) to evaluate ATRX expression in different grades and subtypes of gliomas and correlate with other hallmark genetic alterations, (2) to identify and characterize mosaic/heterogeneous staining in gliomas in terms of mutation status. One hundred seventy six cases of glioma were assessed for ATRX immunohistochemistry and subdivided into positive, negative and mosaic/heterogeneous staining patterns. Five cases with heterogeneous staining were further subjected to next generation sequencing. Higher frequency of ATRX immune-negativity was detected in grade II/III astrocytic, oligoastrocytic tumors and secondary glioblastomas (GBMs), while infrequent in primary GBMs and rare in oligodendrogliomas. Loss of expression was significantly associated with IDH1 and/or TP53 mutation, while mutually exclusive with 1p/19q codeletion. Mosaic/heterogeneous staining was detected exclusively in GBMs (21.2%). Two different types of mosaic staining were identified (1) Admixture of positive and negative nuclei or intermixed mosaic and (2) Separate fragments with positive and negative/intermixed mosaic staining. ATRX mutation was identified in 2/5 (40%) cases with mosaic staining while one case showed DAXX mutation. All these cases were characterized by distinctly separate immune-negative and positive/intermixed foci. Hence, it is suggested that cases with heterogeneous staining (especially those with distinctly negative fragments) should be subjected to mutation analysis.
（1）评估ATRX在不同级别和亚型胶质瘤中的表达，并与其他标志性基因改变相关联；（2）根据突变状态识别并表征胶质瘤中的镶嵌/异质性染色。对176例胶质瘤病例进行了ATRX免疫组化评估，并分为阳性、阴性和镶嵌/异质性染色模式。对5例异质性染色病例进一步进行二代测序。在II/III级星形细胞瘤、少突星形细胞瘤和继发性胶质母细胞瘤（GBM）中检测到较高频率的ATRX免疫阴性，而在原发性GBM中频率较低，在少突胶质细胞瘤中罕见。表达缺失与IDH1和/或TP53突变显著相关，而与1p/19q共缺失相互排斥。仅在GBM中检测到镶嵌/异质性染色（21.2%）。识别出两种不同类型的镶嵌染色：（1）阳性和阴性细胞核混合或混合镶嵌；（2）具有阳性和阴性/混合镶嵌染色的单独片段。在2/5（40%）例镶嵌染色病例中鉴定出ATRX突变，1例显示DAXX突变。所有这些病例的特征是免疫阴性和阳性/混合灶明显分开。因此，建议对异质性染色病例（尤其是那些有明显阴性片段的病例）进行突变分析。
