title: Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential therapeutic target in small-cell lung cancer.
abstract: Small-cell lung cancer (SCLC) comprises about 13-15% of all lung cancers, and more than 29 400 new cases have been diagnosed in the United States in the year 2012. SCLC is a biologically complex tumor typically occurring in heavy smokers. Its medical treatment has almost remained unchanged over the last decades and selected treatment options have not been established so far, mainly due to the lack of targetable genetic alterations. In this study we analyzed a cohort of 307 SCLC samples for fibroblast growth factor receptor 1 (FGFR1) amplification using a dual color FISH probe. FGFR1 status was correlated with clinical data. FGFR1 amplifications were observed in 5.6% of evaluable pulmonary SCLCs. Most of them (93%) fulfilled the criteria for high-level amplification and only one case showed low-level amplification. Amplification patterns were homogenous in the entire tumor area without occurrence of any 'hot spot' areas. FGFR1 amplification status was not associated with age, sex, stage, smoking status or overall survival. FGFR1 amplification analysis by FISH analysis in SCLC is, under respect of certain technical issues, applicable in the routine clinical setting. However, the FGFR1 amplification patterns in SCLC differs strongly from the previously described FGFR1 amplification pattern in squamous cell carcinoma of the lung, as positive SCLC harbor mostly homogeneous high-level amplifications. We provide evidence that an estimated number of 1640 newly diagnosed FGFR1-positive SCLC cases in the United States annually could benefit from targeted therapy. Therefore, we recommend including SCLC in the screening for ongoing clinical trials with FGFR1 inhibitors.
authors.affiliation: 1] Institute of Pathology, University Hospital Cologne, Cologne, Germany [2] Center for Integrated Oncology Cologne/Bonn, Cologne, Germany.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Schultheis
authors.affiliation: 1] Center for Integrated Oncology Cologne/Bonn, Cologne, Germany [2] Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Bos
authors.affiliation: 1] Institute of Pathology, University Hospital Cologne, Cologne, Germany [2] Institute of Pathology, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Schmitz
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Wilsberg
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Binot
authors.affiliation: 1] Center for Integrated Oncology Cologne/Bonn, Cologne, Germany [2] Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
authors.affiliation: 1] Institute of Pathology, University Hospital Cologne, Cologne, Germany [2] Center for Integrated Oncology Cologne/Bonn, Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.affiliation: 1] Institute of Pathology, University Hospital Cologne, Cologne, Germany [2] Center for Integrated Oncology Cologne/Bonn, Cologne, Germany [3] Institute of Pathology, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1