title: ATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset.
abstract: 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.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Suvendu
authors.initials: S
authors.lastname: Purkait
authors.affiliation: McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Miller
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Pathak
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Prerana
authors.initials: P
authors.lastname: Jha
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.affiliation: Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Suri
authors.affiliation: Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Sharma
authors.affiliation: McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fulton
authors.affiliation: Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Shashank Sharad
authors.initials: SS
authors.lastname: Kale
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Sonika
authors.initials: S
authors.lastname: Dahiya
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000075924:X-linked Nuclear Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: ATRX; Glioma; heterogeneous staining; mosaic staining
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