Open AccessATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset
Author(s) -
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
Publication year - 2017
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12364
Subject(s) - atrx , staining , immunohistochemistry , biology , glioma , pathology , death associated protein 6 , mutation , cancer research , genetics , medicine , gene , immunology , nuclear protein , transcription factor
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.