title: High rate of FGFR1 amplifications in brain metastases of squamous and non-squamous lung cancer.
abstract: OBJECTIVE
  FGFR1 amplifications are common in squamous cell carcinoma and rare in adenocarcinoma of the lung, but have not been investigated in brain metastases of non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We performed fluorescent in situ hybridization (FISH) for FGFR1 and immunohistochemistry for pAKT, PI3K, HIF1a and Ki67 in 175 NSCLC brain metastases and 11 matched primary tumors. ALK gene rearrangement status was available from a previous study. We performed statistical correlations of clinical, histopathological and molecular data.
  
  
  RESULTS
  FGFR1 amplifications were found in a total of 30/175 (17%) brain metastases: 4/21 (19%) squamous cell carcinomas, 20/130 (15.3%) adenocarcinomas, 2/12 (16.6%) adenosquamous carcinomas, 4/9 (44.4%) large cell carcinomas and 0/3 neuroendocrine large cell carcinoma. FGFR1 gene status was identical between primary tumors and brain metastases in 9/11 evaluable cases. In 2/11 cases (1 adenosquamous and 1 large cell carcinoma), FGFR1 amplifications were present only in the brain metastasis and not in the primary tumor. Furthermore, we found a significant positive correlation of ALK and FGFR1 gene amplification status in brain metastases (p<0.001, Chi square test). Patients with high-level FGFR1 amplifications had significantly higher number of visceral metastases (p<0.001, Chi square test).
  
  
  CONCLUSIONS
  Our findings argue for an enrichment of FGFR1 amplifications in brain metastases of adenocarcinomas (where they were 5-fold more frequent than reported for primary tumors) and possibly also of other non-squamous carcinomas, but not in squamous cell carcinomas of the lung. These results may be relevant for targeted therapy and prophylaxis of NSCLC brain metastases.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.affiliation: Institute of Cancer Research, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Aysegül
authors.initials: A
authors.lastname: Ilhan-Mutlu
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Carina
authors.initials: C
authors.lastname: Dinhof
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Widhalm
authors.affiliation: Department of Radiotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckmann
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Wöhrer
authors.affiliation: Austrian National Cancer Registry, Statistics Austria, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Hackl
authors.affiliation: Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, and Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria.
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. Electronic address: peter.birner@meduniwien.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D003937:Diagnosis, Differential; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Brain metastases; FGFR1; Fluorescent in situ hybridization; Gene amplification; Lung cancer