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Prognostic significance of histomolecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the ‘integrated’ diagnosis approach
  1. K S Rajmohan1,
  2. Harsha S Sugur1,
  3. S D Shwetha1,
  4. Arvind Ramesh1,
  5. Kandavel Thennarasu2,
  6. Paritosh Pandey3,
  7. Arimappamagan Arivazhagan3,
  8. Vani Santosh1
  1. 1Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
  2. 2Department of Biostatistics, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
  3. 3Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
  1. Correspondence to Professor Vani Santosh, Department of Neuropathology, NIMHANS, Post Bag: 2900, Hosur Road, Bangalore 560029, Karnataka, India; vani.santosh{at}gmail.com

Abstract

Aims Anaplastic gliomas (AGs; WHO Grade III) include anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) and are known to have variable prognosis. Since biomarkers have a major impact on prognosis of gliomas, we compared the prognostic significance of the established biomarkers of AGs and the ‘histomolecular’ subgroups based on the proposed International Society of Neuropathology-Haarlem (‘ISN-Haarlem’) guidelines, with the current WHO 2007 classification.

Methods The study was carried out on formalin-fixed paraffin-embedded (FFPE) tissues from 91 adult patients with AG. Clinical, histological and molecular parameters, including 1p/19q codeletion, isocitrate dehydrogenase gene (IDH1)-R132H positivity, α thalassemia/mental retardation syndrome X-linked gene (ATRX) expression and O6-methylguanine-DNA-methyltransferase gene (MGMT) promoter methylation (mMGMT), were correlated with overall survival (OS) and recurrence-free survival (RFS). Subsequently, following sequencing for rare IDH mutations, we derived three ‘histomolecular’ subgroups based on the ‘integrated’ diagnosis approach proposed by ‘ISN-Haarlem’ guidelines and correlated this with clinical outcome.

Results Gross tumour resection, administration of radiochemotherapy, 1p/19q codeletion, IDH1-R132H positivity and mMGMT were associated with favourable OS and RFS (p≤0.001), while the WHO histological subgroups were prognostically not significant. The ISN ‘histomolecular’ subgroups prognosticated best with AOs (IDHmut, 1p/19q codeleted, ATRX predominantly retained) having the best survival, followed by the AAs (IDHmut, ATRX loss or retained, 1p19q non-codeleted) and AA IDH wild type group having the worst OS and RFS (p=<0.001 for OS).

Conclusions Our study reiterates the prognostic significance of biomarkers, 1p/19q codeletion, IDH1-R132H positivity and mMGMT in AGs. Importantly, we show that the ‘histomolecular’ subgroups of AGs based on the ‘integrated’ diagnosis has a prognostic value, superior to the WHO histological classification.

  • BRAIN TUMOURS
  • FISH
  • IMMUNOHISTOCHEMISTRY
  • MOLECULAR PATHOLOGY
  • NEURO-ONCOLOGY

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