PMID- 29285491
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220311
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 5
IP  - 23
DP  - 2017 Dec
TI  - Detection of MET amplification in gastroesophageal tumor specimens using IQFISH.
PG  - 458
LID - 10.21037/atm.2017.09.07 [doi]
LID - 458
AB  - BACKGROUND: The gene mesenchymal epithelial transition factor (MET) is a 
      proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine 
      kinase activity known as Met or cMet. MET is found to be amplified in several 
      human cancers including gastroesophageal cancer. METHODS: Here we report the MET 
      amplification prevalence data from 159 consecutive tumor specimens from patients 
      with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) 
      adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, 
      MET/CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]. MET 
      amplification was defined as a MET/CEN-7 ratio >/=2.0. Furthermore, the link 
      between the MET signal distribution and amplification status was investigated. 
      RESULTS: The prevalence of MET amplification was found to be 6.9%. The FISH assay 
      demonstrated a high inter-observer reproducibility. The inter-observer results 
      showed a 100% overall agreement with respect to the MET status 
      (amplified/non-amplified). The inter-observer CV was estimated to 11.8% (95% CI: 
      10.2-13.4). For the signal distribution, the inter-observer agreement was 
      reported to be 98.7%. We also report an association of MET amplification and a 
      unique signal distribution pattern in the G/GEJ/E tumor specimens. We found that 
      the prevalence of MET amplification was markedly higher in tumors specimens with 
      a heterogeneous (66.7%) versus homogeneous (2.0%) signal distribution. 
      Furthermore, specimens with a heterogeneous signal distribution had a statically 
      significantly higher median MET/CEN-7 ratio (2.35 versus 1.04; P<0.0001). 
      CONCLUSIONS: The novel FISH assay showed a high inter-observer reproducibility 
      both with respect to amplification status and signal distribution. Based on the 
      finding in the study it is suggested that MET amplification mainly is associated 
      with tumor cells that is represented by a heterogonous growth pattern.
FAU - Jorgensen, Jan Trost
AU  - Jorgensen JT
AD  - Department of Companion Diagnostic Research, Dx-Rx Institute, Fredensborg, 
      Denmark.
FAU - Nielsen, Karsten Bork
AU  - Nielsen KB
AD  - R&D, Diagnostics and Genomics Group, Agilent Technologies Denmark Aps, Glostrup, 
      Denmark.
FAU - Mollerup, Jens
AU  - Mollerup J
AD  - R&D, Diagnostics and Genomics Group, Agilent Technologies Denmark Aps, Glostrup, 
      Denmark.
FAU - Jepsen, Anna
AU  - Jepsen A
AD  - R&D, Diagnostics and Genomics Group, Agilent Technologies Denmark Aps, Glostrup, 
      Denmark.
FAU - Go, Ning
AU  - Go N
AD  - Medical Sciences, Amgen Inc., Thousand Oaks, CA, USA.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC5733332
OTO - NOTNLM
OT  - Mesenchymal epithelial transition factor (MET)
OT  - amplification
OT  - fluorescence in situ hybridization (FISH)
OT  - gastroesophageal cancer
OT  - reproducibility
OT  - signal distribution
COIS- Conflicts of Interest: N Go is an employee of Amgen. KB Nielsen, J Mollerup, and 
      A Jepsen are employees of Agilent Technologies. JT Jorgensen has worked as a 
      consultant for Agilent Technologies, Euro Diagnostica, and Oncology Ventures and 
      has given lectures at meetings sponsored by AstraZeneca, Merck Sharp & Dohme, and 
      Roche.
EDAT- 2017/12/30 06:00
MHDA- 2017/12/30 06:01
PMCR- 2017/12/01
CRDT- 2017/12/30 06:00
PHST- 2017/12/30 06:00 [entrez]
PHST- 2017/12/30 06:00 [pubmed]
PHST- 2017/12/30 06:01 [medline]
PHST- 2017/12/01 00:00 [pmc-release]
AID - atm-05-23-458 [pii]
AID - 10.21037/atm.2017.09.07 [doi]
PST - ppublish
SO  - Ann Transl Med. 2017 Dec;5(23):458. doi: 10.21037/atm.2017.09.07.