Prognostic significance of histomolecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the 'integrated' diagnosis approach.

Autor:	Rajmohan KS; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India., Sugur HS; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India., Shwetha SD; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India., Ramesh A; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India., Thennarasu K; Department of Biostatistics, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India., Pandey P; Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India., Arivazhagan A; Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India., Santosh V; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
Jazyk:	angličtina
Zdroj:	Journal of clinical pathology [J Clin Pathol] 2016 Aug; Vol. 69 (8), pp. 686-94. Date of Electronic Publication: 2016 Jan 07.
DOI:	10.1136/jclinpath-2015-203456
Abstrakt:	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 (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. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
Databáze:	MEDLINE
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