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Oncotarget. 2018 Aug 14;9(63):32204-32218. doi: 10.18632/oncotarget.25941. eCollection 2018 Aug 14.

FGFR3 mRNA overexpression defines a subset of oligometastatic colorectal cancers with worse prognosis.

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Institute of Pathology, University Hospital Göttingen, Göttingen, Germany.
Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.
Targos Molecular Pathology Inc., Kassel, Germany.
Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Georg-August-University, Goettingen, Germany.
Department for Hematology and Medical Oncology, University Hospital Göttingen, Göttingen, Germany.



Metastatic colorectal cancer (CRC) remains a leading cause of cancer related deaths. Patients with oligometastatic liver disease represent a clinical subgroup with heterogeneous course. Until now, biomarkers to characterize outcome and therapeutic options have not been fully established.


We investigated the prevalence of FGFR alterations in a total of 140 primary colorectal tumors and 63 liver metastases of 55 oligometastatic CRC patients. FGF receptors (FGFR1-4) and their ligands (FGF3, 4 and 19) were analyzed for gene amplifications and rearrangements as well as for RNA overexpression in situ. Results were correlated with clinico-pathologic data and molecular subtypes.


Primary tumors showed FGFR1 (6.3%) and FGF3,4,19 (2.2%) amplifications as well as FGFR1 (10.1%), FGFR2 (5.5%) and FGFR3 (16.2%) overexpression. In metastases, we observed FGFR1 amplifications (4.8%) as well as FGFR1 (8.5%) and FGFR3 (14.9%) overexpression. Neither FGFR2-4 amplifications nor gene rearrangements were observed. FGFR3 overexpression was significantly associated with shorter overall survival in metastases (mOS 19.9 vs. 47.4 months, HR=3.14, p=0.0152), but not in primary CRC (HR=1.01, p=0.985). Although rare, also FGFR1 amplification was indicative of worse outcome (mOS 12.6 vs. 47.4 months, HR=8.83, p=0.00111).


We provide the so far most comprehensive analysis of FGFR alterations in primary and metastatic CRC. We describe FGFR3 overexpression in 15% of CRC patients with oligometastatic liver disease as a prognosticator for poor outcome. Recently FGFR3 overexpression has been shown to be a potential therapeutic target. Therefore, we suggest focusing on this subgroup in upcoming clinical trials with FGFR-targeted therapies.


FGFR3; RNA in situ hybridization; colorectal cancer; fibroblast growth factor receptors; metastases

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that there are no competing interests.

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