title: A new bright-field dual-colour chromogenic and silver in situ hybridization method for the detection of FGFR1 gene copy number status.
abstract: Recently, the fibroblast growth factor receptor 1 (FGFR1) has been identified as the first actionable target in squamous cell lung cancer. Clinical trials testing specific FGFR inhibitors are in progress, and patients are selected based on their FGFR1 gene copy number status. Fluorescent in situ hybridization is the most commonly used method for detecting FGFR1 amplifications, but it has its limitations. In this paper, we describe a new non-fading and easy to assess assay for detecting FGFR1 amplification using a combination of chromogenic and silver in situ hybridization. We assessed 394 patients diagnosed with head and neck squamous cell carcinoma with the new assay and compared the results with those obtained by FGFR1 fluorescent in situ hybridization. We could assess copy number by the fluorescent in situ hybridization in 86.8 % (342/394) of cases, whereas with chromogenic and silver in situ hybridization, this was 79.4 % (313/394). By fluorescent in situ hybridization, a FGFR1 amplification was detected in 12.6 % (43/342) of cases, a low-level amplification (LLA) in 7.6 % (26/342) and a high-level amplification (HLA) in 5.0 % (17/342). By chromogenic and silver in situ hybridization, a FGFR1 amplification was found in 10.2 % (32/313) (5.7 % LLA, 4.5 % HLA). The two techniques showed highly concordant results (Pearson's correlation coefficient = 0.971, p < 0.01).
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Boehm
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.forename: Alina
authors.initials: A
authors.lastname: Franzen
authors.forename: Andreas
authors.initials: A
authors.lastname: Schrock
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Heaseley
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018628:Gene Dosage; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D046888:Tissue Array Analysis
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1