Publication: ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patients
Authors
Shao, Li-Wei ; Pan, Yi ; Qi, Xue-Ling ; Ma, Xiao Long ; Yi, Wei-Ning ; Zhang, Jing ; Zhong, Yan-Feng ; Chang, Qing
item.page.secondaryauthor
item.page.director
Publisher
Universidad de Murcia. Departamento de BiologĂa Celular e HistologĂa
publication.page.editor
publication.page.department
DOI
10.14670/HH-11-664
item.page.type
info:eu-repo/semantics/article
Description
Abstract
Background: 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.
publication.page.subject
Citation
Histology and Histopathology, vol.31, nÂş 1, (2016)
item.page.embargo
Ir a EstadĂsticas
Este Ătem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/