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ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patients

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dc.contributor.authorShao, Li-Wei
dc.contributor.authorPan, Yi
dc.contributor.authorQi, Xue-Ling
dc.contributor.authorMa, Xiao Long
dc.contributor.authorYi, Wei-Ning
dc.contributor.authorZhang, Jing
dc.contributor.authorZhong, Yan-Feng
dc.contributor.authorChang, Qing
dc.date.accessioned2021-03-15T09:39:30Z
dc.date.available2021-03-15T09:39:30Z
dc.date.issued2016
dc.description.abstractBackground: IDH1/2 mutation, 1p/19qcodeletion and MGMT hypermethylation are well known molecular markers for gliomas. ATRX and p53 alterations are two lineage-specific genetic aberrations in diffuse astrocytic tumors. The aim of the present study is to clarify the significance of ATRX loss and its correlation with p53 overexpression, IDH1/2 mutations, 1p/19q-codeletion and MGMT hypermethylation in supertentorial astrocytoma, and to determine the prognostic value of these factors in Chinese patients. Methods and Results: A total of 135 adult supertentorial astrocytomas were evaluated. ATRX loss was detected by immunohistochemistry (IHC) and was shown to be much less frequent in pGBs (3.5%) than in grade II, III astrocytomas and IV sGBs (31%). Direct sequencing and/or IHC analysis of the IDH1R132H gene mutation and p53 accumulation demonstrated correlation with age. Strong correlations were found between ATRX loss and IDH1R132H mutation, p53 overexpression as well as MGMT hypermethylation. 1p/19q-codeletion detected by fluorescence in situ hybridization (FISH) showed mutually exclusive with ATRX loss and p53 accumulation. In addition, patients with p53 overexpression combined with ATRX alterations demonstrated substantially longer survival than patients with wild-type ATRX. Conclusions: There may be interactions among these distinct molecules in astrocytoma development. ATRX loss may predict better clinical outcome in astrocytoma patients with p53 overexpression as compared to patients with wild-type ATRX. Tumors with astrocytoma phenotype accompanied by 1p/19q-codeletion and IDH1R132H mutation are mutually exclusive with ATRX and p53 alterations. Routine IHC can be used for evaluation of ATRX loss, p53 protein accumulation and IDH1R132H mutation, which may allow a means of classification of astrocytoma outcome.es
dc.formatapplication/pdfes
dc.format.extent12es
dc.identifier.citationHistology and Histopathology, vol.31, nÂş 1, (2016)
dc.identifier.doi10.14670/HH-11-664
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/104928
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de BiologĂ­a Celular e HistologĂ­aes
dc.relationSin financiaciĂłn externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectATRXes
dc.subjectp53es
dc.subjectIDH1es
dc.subjectMGMTes
dc.subjectImmunohistochemistryes
dc.subjectFluorescence in situ hybridizationes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - PatologĂ­a. Medicina clĂ­nica. OncologĂ­aes
dc.titleATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patientses
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.31, nÂş1 (2016)