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

Nevisi, Fatemeh; Yaghmaie, Marjan; Pashaiefar, Hossein; Alimoghaddam, Kamran; Iravani, Masoud; Javadi, Gholamreza; Ghavamzadeh, Ardeshir

doi:10.29252/ibj.24.1.47

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

Authors

Fatemeh Nevisi ¹

Marjan Yaghmaie ²

Hossein Pashaiefar ²

Kamran Alimoghaddam ²

Masoud Iravani ³

Gholamreza Javadi ¹

Ardeshir Ghavamzadeh ²

¹ Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

² Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran

³ Masood GI and Hepatology Clinic, Tehran, Iran

10.29252/ibj.24.1.47

Abstract

Background: The analysis of the gene copy number alterations in tumor samples are increasingly used for diagnostic and prognostic purposes in patients with gastric cancer (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 circulating tumor cells (CTCs) 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 CTCs and matched biopsy tissues from 37 GC patients using fluorescence in situ hybridization. Results: HER2 amplification was observed in 2 (5.41%) samples. HER2 gene status in CTCs 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 CTCs isolated from this patient. c-MYC amplification was observed in 3 (8.11%) samples, and the status of its amplification in the CTCs 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 CTCs and achieved biopsies, and, consequently, CTC may act as a non-invasive alternative for recording the amplification of these genes among GC patients.

Keywords

Circulating tumor cells

Fluorescence in situ hybridization

Gene Amplification