title: FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non-small cell lung cancer.
abstract: This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non-small cell lung cancer (NSCLC). Additionally, a screen to define the frequency ofFGFR3-TACC3translocation andFGFR3amplification was performed. Archived tissues from 653 NSCLC samples (adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC)) were analysed with immunohistochemistry (IHC) for expression of FGFR1, 2 and 3. Expression levels of FGFR1, 2 and 3 were correlated with clinicopathological features. The presence ofFGFR3-TACC3translocation was detected by RT-PCR andFGFR3amplification was detected by fluorescencein situhybridization. FGFR1, 2 and 3 proteins were highly expressed in 64 (10.6%), 76 (12.9%) and 20 (3.3%) NSCLC tumour samples, respectively. Protein expression of FGFR1 was significantly related to worse overall survival in NSCLC. Furthermore, FGFR1 protein expression was associated with light smoking and histological subtype (AC), FGFR2 protein expression with female gender, younger age, histological subtype (AC) and lower tumour stage, and FGFR3 protein was significantly overexpressed in tumours of older patients and SCC histology. TheFGFR3-TACC3fusion was detected in 3.0% (6/200) of NSCLC samples and theFGFR3gene was amplified in 4.7% of IHC positive NSCLC samples (2/43). FGFR1, 2 and 3 proteins are expressed in a high number of early stage NSCLC and FGFR1 protein expression may serve as a prognostic biomarker. Recurrent translocations and amplifications inFGFR3can be found in NSCLC. This study shows that FGFR family members are frequently aberrant in NSCLC and could be interesting therapeutic targets for the treatment of NSCLC.
authors: Department of Thoracic Oncology The Netherlands Cancer Institute Amsterdam The Netherlands.
authors: Willemijn Sme
authors: WS
authors: Theelen
authors: Division of Molecular Carcinogenesis The Netherlands Cancer Institute Amsterdam The Netherlands.
authors: Lorenza
authors: L
authors: Mittempergher
authors: Department of Pathology University Medical Center Utrecht Utrecht The Netherlands.
authors: Stefan M
authors: SM
authors: Willems
authors: Division of Molecular Carcinogenesis The Netherlands Cancer Institute Amsterdam The Netherlands.
authors: Astrid J
authors: AJ
authors: Bosma
authors: Core Facility Molecular Pathology & Biobanking, Department of Molecular Pathology The Netherlands Cancer Institute Amsterdam The Netherlands.
authors: Dennis Dgc
authors: DD
authors: Peters
authors: Department of Biometrics The Netherlands Cancer Institute The Netherlands.
authors: Vincent
authors: V
authors: van der Noort
authors: Department of Pulmonology OLVG Amsterdam The Netherlands.
authors: Eva J
authors: EJ
authors: Japenga
authors: Department of Pathology University Medical Center Utrecht Utrecht The Netherlands.
authors: Ton
authors: T
authors: Peeters
authors: Department of Pathology University Medical Center Utrecht Utrecht The Netherlands.
authors: Koos
authors: K
authors: Koole
authors: Division of Molecular Carcinogenesis The Netherlands Cancer Institute Amsterdam The Netherlands.
authors: Tonći
authors: T
authors: Šuštić
authors: Department of Pathology OLVG Amsterdam The Netherlands.
authors: J L
authors: JL
authors: Blaauwgeers
authors: Department of Pathology Academic Medical Center Amsterdam The Netherlands.
authors: Carel J
authors: CJ
authors: van Noesel
authors: Division of Molecular Carcinogenesis The Netherlands Cancer Institute Amsterdam The Netherlands.
authors: René
authors: R
authors: Bernards
authors: Department of Thoracic Oncology The Netherlands Cancer Institute Amsterdam The Netherlands.
authors: Michel M
authors: MM
authors: van den Heuvel
keywords: FGFR3 amplification; FGFR3‐TACC3 translocation; fibroblast growth factor receptor (FGFR); immunohistochemistry (IHC); non‐small cell lung cancer (NSCLC)