Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas.
Neuro Oncol
; 19(9): 1206-1216, 2017 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-28379477
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Biomarkers, Tumor
/
Receptor, Fibroblast Growth Factor, Type 3
/
Glioma
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Neuro Oncol
Journal subject:
NEOPLASIAS
/
NEUROLOGIA
Year:
2017
Document type:
Article