Correlation of HER2, MDM2, c-MYC, c-MET, and TP53 Copy Number Alterations in Circulating Tumor Cells with Tissue in Gastric Cancer Patients: A Pilot Study

Abstract

Background:The analysis of the gene copy number alterations in tumor samples are increasingly used for diagnostic and prognostic purposes in patients with GC. However, these procedures are not always applicable due to their invasive nature. In this study, we have analyzed the copy number alterations of five genes (HER2, MDM2, c-MYC, c-MET, and TP53) with a fixed relevance for GC in the CTC of GC patients, and, accordingly, as a potential approach, evaluated their usage to complete primary tumor biopsy. Methods:We analyzed the status of the copy number alterations of the selected genes in CTC and matched biopsy tissues from 37 GC patients using FISH. Results: HER2 amplification was observed in 2 (5.41%) samples. HER2 gene status in CTC showed a strong agreement with its status in 36 out of 37 patients’ matched tissue samples (correlation: 97.29%; Kappa: 0.65; p < 0.001). MDM2 amplification was found only in 1 (2.70%) sample; however, the amplification of this gene was not detectable in the CTC isolated from this patient. c-MYC amplification was observed in 3 (8.11%) samples, and the status of its amplification in the CTC indicated a complete agreement with its status in the matched tissue samples (correlation: 100%; Kappa: 1.0). Conclusion:Our work suggests that the amplification of HER2 and c-MYC is in concordance with the CTC and achieved biopsies, and, consequently, CTC may act as a non-invasive alternative for recording the amplification of these genes among GC patients.