Jørgensen Jan Trøst, Nielsen Karsten Bork, Mollerup Jens, Jepsen Anna, Go Ning
Department of Companion Diagnostic Research, Dx-Rx Institute, Fredensborg, Denmark.
R&D, Diagnostics and Genomics Group, Agilent Technologies Denmark Aps, Glostrup, Denmark.
Ann Transl Med. 2017 Dec;5(23):458. doi: 10.21037/atm.2017.09.07.
The gene mesenchymal epithelial transition factor () is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. is found to be amplified in several human cancers including gastroesophageal cancer.
Here we report the 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, /CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]. amplification was defined as a /CEN-7 ratio ≥2.0. Furthermore, the link between the MET signal distribution and amplification status was investigated.
The prevalence of 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 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 amplification and a unique signal distribution pattern in the G/GEJ/E tumor specimens. We found that the prevalence of 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 /CEN-7 ratio (2.35 versus 1.04; P<0.0001).
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 amplification mainly is associated with tumor cells that is represented by a heterogonous growth pattern.
间充质上皮转化因子（）基因是一种原癌基因，编码一种具有内在酪氨酸激酶活性的跨膜受体，称为Met或cMet。在包括胃食管癌在内的几种人类癌症中发现该基因存在扩增。
在此，我们报告了使用一种新型荧光原位杂交（FISH）检测方法，即/CEN-7 IQFISH探针混合物[仅用于研究用途（IUO）检测]，对159例连续的胃（G）、胃食管交界（GEJ）和食管（E）腺癌患者的肿瘤标本进行的扩增患病率数据。扩增定义为/CEN-7比值≥2.0。此外，还研究了MET信号分布与扩增状态之间的联系。
发现扩增患病率为6.9%。FISH检测显示观察者间具有较高的重复性。观察者间结果在状态（扩增/未扩增）方面总体一致性为100%。观察者间CV估计为11.8%（95%CI：10.2 - 13.4）。对于信号分布，观察者间一致性报告为98.7%。我们还报告了在G/GEJ/E肿瘤标本中扩增与独特信号分布模式之间的关联。我们发现，信号分布异质性（66.7%）的肿瘤标本中扩增患病率明显高于均匀性（2.0%）的标本。此外，信号分布异质性标本的/CEN-7比值中位数在统计学上显著更高（2.35对1.04；P<0.0001）。
新型FISH检测在扩增状态和信号分布方面均显示出较高的观察者间重复性。基于该研究结果，提示扩增主要与以异质性生长模式为代表的肿瘤细胞相关。
