Prognostic significance of histomolecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the 'integrated' diagnosis approach. Issue 8 (7th January 2016)

• Record Type: Journal Article
• Authors: Rajmohan, K S; Sugur, Harsha S; Shwetha, S D; Ramesh, Arvind; Thennarasu, Kandavel; Pandey, Paritosh; Arivazhagan, Arimappamagan; Santosh, Vani
• Is Part Of: Journal of clinical pathology. Volume 69:Issue 8(2016)
• Page Start: 686
• Page End: 694
• Publication Date: 2016-01-07
• Subjects: BRAIN TUMOURS -- FISH -- IMMUNOHISTOCHEMISTRY -- MOLECULAR PATHOLOGY -- NEURO-ONCOLOGY; Pathology -- Periodicals; Pathology, Molecular -- Periodicals; 616.0705
• DOI: 10.1136/jclinpath-2015-203456
• Languages: English
• ISSNs: 0021-9746

Abstract

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 O 6 -methylguanine-DNA-methyltransferase gene ( MGMT ) promoter methylation (m MGMT ), 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 m MGMT 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 ( IDH mut, 1p/19q codeleted, ATRX predominantly retained) having the best survival, followed by the AAs ( IDH mut, 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 m MGMT 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.