TY - JOUR
T1 - A new bright-field dual-colour chromogenic and silver in situ hybridization method for the detection of FGFR1 gene copy number status
AU - Boehm, Diana
AU - Vogel, Wenzel
AU - Franzen, Alina
AU - Schrock, Andreas
AU - Bootz, Friedrich
AU - Heaseley, Lynn E.
AU - Braun, Martin
AU - Perner, Sven
N1 - Funding Information:
Conflict of interest This study was supported financially and technically by Ventana (Ventana Medical Systems, Tucson, AZ) as well as by a grant of the Rudolf Becker-Foundation (to SP). Ventana had no role in the design of the study. Experiments, assessment and interpretation of the data were performed by the authors themselves.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/5
Y1 - 2014/5
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=84902318218&partnerID=8YFLogxK
U2 - 10.1007/s00428-014-1564-z
DO - 10.1007/s00428-014-1564-z
M3 - Journal articles
C2 - 24584974
AN - SCOPUS:84902318218
SN - 0945-6317
VL - 464
SP - 547
EP - 551
JO - Virchows Archiv
JF - Virchows Archiv
IS - 5
ER -