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Expression of neurodegenerative disease‐related proteins and caspase‐3 in glioneuronal tumours
Author(s) -
Prabowo A. S.,
Iyer A. M.,
Veersema T. J.,
Anink J. J.,
Schoutenvan Meeteren A. Y. N.,
Spliet W. G. M.,
Rijen P. C.,
Ferrier C. H.,
Thom M.,
Aronica E.
Publication year - 2015
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12143
Subject(s) - neurodegeneration , caspase 3 , biology , pathology , immunohistochemistry , epilepsy , caspase , ganglioglioma , cancer research , apoptosis , programmed cell death , medicine , disease , neuroscience , biochemistry
Aims Recent evidence supports the activation of mechanisms underlying cellular ageing and neurodegeneration in developmental lesions associated with epilepsy. The present study examined the ongoing cell injury and vulnerability to neuronal degeneration in glioneuronal tumours ( GNT ). Methods We evaluated a series of GNT ( n = 31 gangliogliomas, GG and n = 30 dysembryoplastic neuroepithelial tumours, DNT ). Sections were processed for immunohistochemistry using markers for the evaluation of caspase‐3 and neurodegeneration‐related proteins/pathways and their expression was correlated with the tumour features and the clinical history of epilepsy. Results Both GG and DNT specimens contained caspase‐3‐positive cells. In GG , expression of activated caspase‐3 was negatively correlated the with the BRAF V 600 E mutation status. We also observed an abnormal expression of death receptor‐6 and β‐amyloid precursor protein ( APP ). Moreover, dysplastic neurones expressed p62, phosphorylated (p) TDP 43 and pTau . Double labelling experiments showed colocalization of phosphorylated S 6 (marker of mammalian target of rapamycin, mTOR , pathway activation) with pTau and p62. In GG , neuronal p62 expression was positively correlated with pS 6. The immunoreactivity score ( IRS ) of caspase‐3, APP , DR 6, p62 and pTDP 43 were found to be significantly higher in GG than in DNT . Expression of APP , DR 6, pTau (in GG and DNT ) and caspase‐3 (in GG ) positively correlated with duration of epilepsy. In GG , the expression of neuronal caspase‐3, DR 6 and glial p62 was associated with a worse postoperative seizure outcome. Conclusions Our observations in GNT provide evidence of premature activation of mechanisms of neurodegeneration which are associated with the clinical course of epilepsy in patient with GG .