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BMC Cancer. 2017 May 3;17(1):310. doi: 10.1186/s12885-017-3274-9.

Clinical association analysis of ependymomas and pilocytic astrocytomas reveals elevated FGFR3 and FGFR1 expression in aggressive ependymomas.

Author information

1
BioMediTech Institute and Faculty of Medicine and Life Sciences, Biokatu 8, 33520, Tampere, Finland.
2
Fimlab Laboratories Ltd., Tampere University Hospital, Biokatu 4, 33520, Tampere, Finland.
3
Department of Pathology, University of Tampere, 33014, Tampere, Finland.
4
Department of Pediatrics, Tampere University Hospital; Tampere Center for Child Health Research, University of Tampere, 33014, Tampere, Finland.
5
Department of Signal Processing, Tampere University of Technology, Korkeakoulunkatu 10, 33720, Tampere, Finland.
6
Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest Baptist Medical Center, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA.
7
Science Center, Tampere University Hospital, Biokatu 6, 33520, Tampere, Finland.
8
Fimlab Laboratories Ltd., Tampere University Hospital, Biokatu 4, 33520, Tampere, Finland. hannu.haapasalo@fimlab.fi.
9
Department of Pathology, University of Tampere, 33014, Tampere, Finland. hannu.haapasalo@fimlab.fi.
10
BioMediTech Institute and Faculty of Medicine and Life Sciences, Biokatu 8, 33520, Tampere, Finland. kirsi.granberg@uta.fi.
11
Department of Signal Processing, Tampere University of Technology, Korkeakoulunkatu 10, 33720, Tampere, Finland. kirsi.granberg@uta.fi.
12
Science Center, Tampere University Hospital, Biokatu 6, 33520, Tampere, Finland. kirsi.granberg@uta.fi.

Abstract

BACKGROUND:

Fibroblast growth factor receptors (FGFRs) are well-known proto-oncogenes in several human malignancies and are currently therapeutically targeted in clinical trials. Among glioma subtypes, activating FGFR1 alterations have been observed in a subpopulation of pilocytic astrocytomas while FGFR3 fusions occur in IDH wild-type diffuse gliomas, resulting in high FGFR3 protein expression. The purpose of this study was to associate FGFR1 and FGFR3 protein levels with clinical features and genetic alterations in ependymoma and pilocytic astrocytoma.

METHODS:

FGFR1 and FGFR3 expression levels were detected in ependymoma and pilocytic astrocytoma tissues using immunohistochemistry. Selected cases were further analyzed using targeted sequencing.

RESULTS:

Expression of both FGFR1 and FGFR3 varied within all tumor types. In ependymomas, increased FGFR3 or FGFR1 expression was associated with high tumor grade, cerebral location, young patient age, and poor prognosis. Moderate-to-strong expression of FGFR1 and/or FGFR3 was observed in 76% of cerebral ependymomas. Cases with moderate-to-strong expression of both proteins had poor clinical prognosis. In pilocytic astrocytomas, moderate-to-strong FGFR3 expression was detected predominantly in non-pediatric patients. Targeted sequencing of 12 tumors found no protein-altering mutations or fusions in FGFR1 or FGFR3.

CONCLUSIONS:

Elevated FGFR3 and FGFR1 protein expression is common in aggressive ependymomas but likely not driven by genetic alterations. Further studies are warranted to evaluate whether ependymoma patients with high FGFR3 and/or FGFR1 expression could benefit from treatment with FGFR inhibitor based therapeutic approaches currently under evaluation in clinical trials.

KEYWORDS:

Deep-sequencing; FGFR inhibition; Immunohistochemistry staining; Tissue microarray

PMID:
28468611
PMCID:
PMC5415775
DOI:
10.1186/s12885-017-3274-9
[Indexed for MEDLINE]
Free PMC Article

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