Clinical significance of phenotyping and karyotyping of circulating tumor cells in patients with advanced gastric cancer

// Yilin Li 1 , Xiaotian Zhang 1 , Sai Ge 1 , Jing Gao 1 , Jifang Gong 1 , Ming Lu 1 , Qiyue Zhang 1 , Yanshuo Cao 1 , Daisy Dandan Wang 2 , Peter Ping Lin 2 , Lin Shen 1 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University Cancer Hospital & Institute, Beijing, China 2 Cytelligen, San Diego, CA, USA Correspondence: Lin Shen, email: // Keywords : gastric cancer, circulating tumor cells, EpCAM-independent enrichment, HER2, aneuploidy Received : May 20, 2014 Accepted : July 05, 2014 Published : July 07, 2014 Abstract BACKGROUND: Karyotyping and phenotyping of circulating tumor cells (CTCs) in therapeutic cancer patients is of particular clinical significance in terms of both identifying chemo-resistant CTC subtypes and understanding CTC evolution. METHODS: The integrated subtraction enrichment (SET) and immunostaining-fluorescence in situ hybridization (iFISH) platform was applied to detect and characterize CTCs in patients with advanced gastric cancer (AGC). Status of human epidermal growth factor receptor 2 (HER2) expressing and aneuploidy of chromosome 8 in CTCs enriched from the patients was examined by SET-iFISH following clinical chemotherapy or HER2-targeted therapy. CellSearch system was applied as a reference control. RESULTS: Phenotyping of CTCs in HER2 positive AGC patients demonstrated that HER2 + CTCs could be effectively eliminated in response to HER2-targeted therapy. Karyotyping of CTCs indicated that distinct CTCs with different ploidies of chromosomes 8 in AGC patients correlated to either sensitivity or resistance of paclitaxel or cisplatin-based chemotherapy. Examination of the copy number of chromosome 8 in CTCs provides a potential approach for predicting chemotherapeutic efficacy and monitoring chemo-resistance. CONCLUSIONS: Phenotyping and karyotyping of the enriched CTCs upon ploidy of chromosome 8 or HER2 expression is of clinical potential for monitoring chemo-resistance and evaluating therapeutic efficacy for AGC patients.