PT  - JOURNAL ARTICLE
AU  - Rajmohan, K S
AU  - Sugur, Harsha S
AU  - Shwetha, S D
AU  - Ramesh, Arvind
AU  - Thennarasu, Kandavel
AU  - Pandey, Paritosh
AU  - Arivazhagan, Arimappamagan
AU  - Santosh, Vani
TI  - Prognostic significance of histomolecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the ‘integrated’ diagnosis approach
AID  - 10.1136/jclinpath-2015-203456
DP  - 2016 Aug 01
TA  - Journal of Clinical Pathology
PG  - 686--694
VI  - 69
IP  - 8
4099  - http://jcp.bmj.com/content/69/8/686.short
4100  - http://jcp.bmj.com/content/69/8/686.full
SO  - J Clin Pathol2016 Aug 01; 69
AB  - 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.