Format

Send to

Choose Destination
Neuro Oncol. 2017 Sep 1;19(9):1206-1216. doi: 10.1093/neuonc/nox028.

Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas.

Author information

1
BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Department of Signal Processing, Tampere University of Technology, Tampere, Finland; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Science Center, Tampere University Hospital, Tampere, Finland; Fimlab Laboratories Ltd., Tampere University Hospital, Tampere, Finland; Unit of Neurosurgery, Tampere University Hospital, Tampere, Finland; Pori unit, Tampere University of Technology, Pori, Finland; Department of Pathology, University of Tampere, Tampere, Finland; Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.

Abstract

Background:

Inhibitors of fibroblast growth factor receptors (FGFRs) have recently arisen as a promising treatment option for patients with FGFR alterations. Gene fusions involving FGFR3 and transforming acidic coiled-coil protein 3 (TACC3) have been detected in diffuse gliomas and other malignancies, and fusion-positive cases have responded well to FGFR inhibition. As high FGFR3 expression has been detected in fusion-positive tumors, we sought to determine the clinical significance of FGFR3 protein expression level as well as its potential for indicating FGFR3 fusions.

Methods:

We performed FGFR3 immunohistochemistry on tissue microarrays containing 676 grades II-IV astrocytomas and 116 grades II-III oligodendroglial tumor specimens. Fifty-one cases were further analyzed using targeted sequencing.

Results:

Moderate to strong FGFR3 staining was detected in gliomas of all grades, was more common in females, and was associated with poor survival in diffuse astrocytomas. Targeted sequencing identified FGFR3-TACC3 fusions and an FGFR3-CAMK2A fusion in 10 of 15 strongly stained cases, whereas no fusions were found in 36 negatively to moderately stained cases. Fusion-positive cases were predominantly female and negative for IDH and EGFR/PDGFRA/MET alterations. These and moderately stained cases show lower MIB-1 proliferation index than negatively to weakly stained cases. Furthermore, stronger FGFR3 expression was commonly observed in malignant tissue regions of lower cellularity in fusion-negative cases. Importantly, subregional negative FGFR3 staining was also observed in a few fusion-positive cases.

Conclusions:

Strong FGFR3 protein expression is indicative of FGFR3 fusions and may serve as a clinically applicable predictive marker for treatment regimens based on FGFR inhibitors.

KEYWORDS:

biomarker; gene fusion; glioblastoma; targeted sequencing

PMID:
28379477
PMCID:
PMC5570261
DOI:
10.1093/neuonc/nox028
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center