title: FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma.
abstract: OBJECTIVE
  Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to multi-kinase inhibitors targeting FGFR1. Esophageal cancer is an aggressive disease, for which novel targeted therapies are highly warranted.
  
  
  METHODS
  This study was designed to investigate the prevalence and clinical significance of FGFR1 amplification in a tissue microarray containing 346 adenocarcinomas and 254 squamous cell carcinomas of the esophagus, using dual-labeling fluorescence in situ hybridization (FISH) analysis.
  
  
  RESULTS
  FGFR1 amplification, defined as a ratio of FGFR1:centromere 8 copy numbers ≥ 2.0, was more frequently seen in squamous cell carcinoma (8.9% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308; p<0.0001). There was no association between FGFR1 amplification and tumor phenotype or clinical outcome. To study potential heterogeneity of FGFR1 amplification, all available tumor blocks from 23 FGFR1 amplified tumors were analyzed on conventional large sections. This analysis revealed complete homogeneity of FGFR1 amplification in 20 (86.9%) primary tumors and in all available lymph node metastases. Remarkably, FGFR1 amplification was also seen in dysplasia adjacent to tumor in 6 of 9 patients with FGFR1 amplified primary cancers.
  
  
  CONCLUSIONS
  In conclusion, FGFR1 amplification occurs in a relevant subgroup of carcinomas of the esophagus and may play a particular role for development of squamous cell cancers. The high homogeneity of FGFR1 amplification suggests that patients with FGFR1 amplified esophageal cancers may particularly benefit from anti-FGFR1 therapies and prompt for clinical studies in this tumor type.
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: von Loga
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jule
authors.initials: J
authors.lastname: Kohlhaussen
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lia
authors.initials: L
authors.lastname: Burkhardt
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Burdak-Rothkamm
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jacobsen
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1