Clinical Research Papers:
Clinical significance of phenotyping and karyotyping of circulating tumor cells in patients with advanced gastric cancer
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Yilin Li1, Xiaotian Zhang1, Sai Ge1, Jing Gao1, Jifang Gong1, Ming Lu1, Qiyue Zhang1, Yanshuo Cao1, Daisy Dandan Wang2, Peter Ping Lin2, Lin Shen1
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
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
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.
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