Low co-expression of epidermal growth factor receptor and its chaperone heat shock protein 90 is associated with worse prognosis in primary glioblastoma, IDH-wild-type.

Détails

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Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_0FF76A277B99
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Low co-expression of epidermal growth factor receptor and its chaperone heat shock protein 90 is associated with worse prognosis in primary glioblastoma, IDH-wild-type.
Périodique
Oncology reports
Auteur⸱e⸱s
Sartori E., Langer R., Vassella E., Hewer E., Schucht P., Zlobec I., Berezowska S.
ISSN
1791-2431 (Electronic)
ISSN-L
1021-335X
Statut éditorial
Publié
Date de publication
10/2017
Peer-reviewed
Oui
Volume
38
Numéro
4
Pages
2394-2400
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Epidermal growth factor receptor (EGFR) is a major oncogenic driver in glioblastoma (GBM) without mutations in the isocitrate dehydrogenase gene (IDH-wildtype). Heat shock protein 90 (HSP90) is a regulator of the stability of oncogenic proteins including EGFR, thereby acting as a molecular chaperone. We investigated the expression of EGFR and its chaperone HSP90 in GBM, IDH-wildtype. Tissue availability permitted analysis of 237/449 consecutive GBM cases, among them 214 IDH-wildtype (90.3%). The expression of EGFR and HSP90 was analysed by immunohistochemistry on a tissue microarray containing various tumour regions. The expression intensity (EI), and an expression score (ES) combining the percentage of stained cells with EI were determined for both markers. Overall, there was a positive correlation between EGFR and HSP90 expression (EI; r=0.275, P<0.001; ES, r=0.333, P<0.001). The expression of EGFR and HSP90 was significantly higher in the tumour centre, compared to the infiltration front (EI, P=0.002; ES, P<0.001). Survival data were available in 96 IDH-wildtype cases, and high expression of EGFR (ES only) was in trend associated with better outcome, but failed to meet statyistical significance (P=0.061). A combination of EGFR and HSP90, however, discriminated between different prognostic groups, with EGFRlow/HSP90low tumours showing the worst prognosis in univariate analysis (P=0.001), and in multivariate analysis including the other relevant prognostic factors age, MGMT status and postoperative treatment [n=76; hazard ratio (HR)=0.571; 95% confidence interval (CI) 0.328-0.996; P=0.048]. EGFR expression stratified most pronounced among HSP90low tumours, where the EGFRhigh phenotype was associated with longer survival. Our results reveal a variable reliance on the signalling pathway by EGFR in GBM, IDH-wildtype. Low co-expression was associated with worse prognosis.
Mots-clé
Adult, Aged, Aged, 80 and over, Disease-Free Survival, ErbB Receptors/genetics, Female, Gene Expression Regulation, Neoplastic, Glioblastoma/genetics, Glioblastoma/pathology, HSP90 Heat-Shock Proteins/genetics, Humans, Isocitrate Dehydrogenase/genetics, Male, Middle Aged, Prognosis
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/06/2020 10:29
Dernière modification de la notice
06/11/2020 15:56
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