title: ATRX loss in glioneuronal tumors with neuropil-like islands indicates similarity to diffuse astrocytic tumors.
abstract: Glioneuronal tumor with neuropil-like islands (GTNI) is a rare, recently described neoplasm, whose pathogenesis has not been studied extensively. The role of ATRX mutations, a class-defining alteration in diffuse astrocytic neoplasms, has not been assessed in GTNIs previously. We therefore aimed to assess the status of ATRX, along with IDH1, 1p/19q and p53, in cases of GTNI in order to evaluate the molecular profile of these tumors. All cases of GTNI diagnosed at our Institute were retrieved and clinicopathological features were reviewed. Immunohistochemistry for ATRX, IDH1 and p53 was performed. We identified four cases of GTNI, majority of which occurred in young adults. Loss of ATRX immunoexpression, a surrogate marker for ATRX mutation, was seen in all four cases. All cases were immunopositive for p53, while IDH1 positivity was seen in all three cases assessed. 1p/19q codeletion was absent in the three cases analyzed. These results indicate that the molecular pathogenesis of GTNIs similar to that of diffuse astrocytic tumors. Further, the loss of ATRX expression is seen in both the glial as well as neuronal components, indicating that both arise from the same tumor stem/progenitor cell and that the latter may be a metaplastic change. Thus, loss of ATRX immunoexpression, shown for the first time in these tumors, along with immunopositivity for p53 and IDH1, indicates that these tumors are molecular astrocytomas, and their clinical behaviour is likely to recapitulate that of ATRX-mutant and IDH-mutant diffuse astrocytomas of the same grade.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Aanchal
authors.initials: A
authors.lastname: Kakkar
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Aruna
authors.initials: A
authors.lastname: Nambirajan
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Kavneet
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Supriya
authors.initials: S
authors.lastname: Mallick
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
authors.affiliation: Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Shashank Sharad
authors.initials: SS
authors.lastname: Kale
authors.affiliation: Department of Neuroradiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Garg
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India. sharmamehar@yahoo.co.in.
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019581:Neuropil / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000075924:X-linked Nuclear Protein / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D000075924:X-linked Nuclear Protein; D010751:Phosphopyruvate Hydratase
keywords: ATRX; Astrocytoma; Brain tumors; Glioma; Glioneuronal tumor with neuropil-like islands; IDH