title: Rationale for treatment of metastatic squamous cell carcinoma of the lung using fibroblast growth factor receptor inhibitors.
abstract: BACKGROUND
  We previously identified amplification of the fibroblast growth factor receptor 1 gene (FGFR1) as a potential therapeutic target for small-molecule inhibitor therapy in squamous cell lung cancer (L-SCC). Currently, clinical phase I trials are underway to examine whether patients with FGFR1-amplified L-SCC benefit from a targeted therapy approach using small-molecule inhibitors. Because most patients with lung cancer present with metastatic disease, we investigated whether lymph node metastases in L-SCC share the FGFR1 amplification status of their corresponding primary tumor.
  
  
  METHODS
  The study cohort consisted of 72 patients with L-SCC, 39 with regional lymph node metastases. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissue of the primary tumors and, where present, of the corresponding lymph node metastasis. A biotin-labeled target probe spanning the FGFR1 locus (8p11.22-23) was used to determine the FGFR1 amplification status by fluorescence in situ hybridization.
  
  
  RESULTS
  FGFR1 amplification was detected in 16% (12 of 72) of all primary L-SCCs. In metastatic tumors, 18% (seven of 39) of the lymph node metastases displayed FGFR1 amplification with an exact correlation of FGFR1 amplification status between tumor and metastatic tissue.
  
  
  CONCLUSIONS
  FGFR1 amplification is a common genetic event occurring at a frequency of 16% in L-SCCs. Moreover, lymph node metastases derived from FGFR1-amplified L-SCCs also exhibit FGFR1 amplification. Therefore, we suggest that the FGFR1 amplification is a clonal event in tumor progression. Beyond this biologically relevant observation, the findings carry potential therapeutic implications in that small-molecule inhibitors may be applicable to the treatment of a subset of patients with metastatic L-SCC.
authors.affiliation: Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Göke
authors.affiliation: Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Franzen
authors.affiliation: Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Roopika
authors.initials: R
authors.lastname: Menon
authors.affiliation: Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Diane
authors.initials: D
authors.lastname: Goltz
authors.affiliation: Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Kirsten
authors.affiliation: Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Boehm
authors.affiliation: Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Antonia
authors.initials: A
authors.lastname: Göke
authors.affiliation: Department of Hematology and Oncology, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Scheble
authors.affiliation: Department of Urology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Department of Thorax Surgery, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gerigk
authors.affiliation: Institute of Pathology, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wagner
authors.affiliation: Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Department of Head and Neck Surgery, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schroeck
authors.affiliation: Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. Electronic address: sven.perner1972@gmail.com.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1