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Ann Transl Med. 2017 Dec;5(23):458. doi: 10.21037/atm.2017.09.07.

Detection of MET amplification in gastroesophageal tumor specimens using IQFISH.

Author information

1
Department of Companion Diagnostic Research, Dx-Rx Institute, Fredensborg, Denmark.
2
R&D, Diagnostics and Genomics Group, Agilent Technologies Denmark Aps, Glostrup, Denmark.
3
Medical Sciences, Amgen Inc., Thousand Oaks, CA, USA.

Abstract

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.

KEYWORDS:

Mesenchymal epithelial transition factor (MET); amplification; fluorescence in situ hybridization (FISH); gastroesophageal cancer; reproducibility; signal distribution

Conflict of interest statement

Conflicts of Interest: N Go is an employee of Amgen. KB Nielsen, J Mollerup, and A Jepsen are employees of Agilent Technologies. JT Jørgensen 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.

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