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

Sartori, Elsa; Langer, Rupert; Vassella, Erik; Hewer, Ekkehard; Schucht, Philippe; Zlobec, Inti; Berezowska, Sabina Anna (2017). 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. Oncology reports, 38(4), pp. 2394-2400. Spandidos Publications 10.3892/or.2017.5863

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
UniBE Contributor:	Langer, Rupert, Vassella, Erik, Hewer, Ekkehard Walter, Schucht, Philippe, Zlobec, Inti, Berezowska, Sabina Anna
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	1021-335X
Publisher:	Spandidos Publications
Language:	English
Submitter:	Ekkehard Hewer
Date Deposited:	04 Oct 2017 11:03
Last Modified:	02 Mar 2023 23:29
Publisher DOI:	10.3892/or.2017.5863
PubMed ID:	28765916
URI:	https://boris.unibe.ch/id/eprint/105060