Weirong Chen1, Juncheng Zhang2, Lijian Huang3, Lin Chen2, Yanling Zhou2, Dongjiang Tang2, Yingming Xie4, Hong Wang5, Chuoji Huang6. 1. Department of Breast Surgery, Zhuhai Maternity and Child Health Hospital, Zhuhai, China. 2. Zhuhai Livzon Cynvenio Diagnostics Ltd, Zhuhai, China; Joint Research Center of Liquid Biopsy in Guangdong, Hong Kong and Macao, China. 3. Department of Oncology, WUYI Traditional Chinese Medicine, Jiangmen, China. 4. The Central Blood Station of Zhuhai, Zhuhai, China. 5. Department of Breast Surgery, Zhuhai Maternity and Child Health Hospital, Zhuhai, China. Electronic address: Wh0019@hotmail.com. 6. Zhuhai Livzon Cynvenio Diagnostics Ltd, Zhuhai, China; Joint Research Center of Liquid Biopsy in Guangdong, Hong Kong and Macao, China. Electronic address: huang.chuoji@livzoncynvenio.cn.
Abstract
BACKGROUND: Most previous studies of circulating tumor cells (CTCs) are based on the CellSearch platform, but CellSearch has a number of limitations. This study aimed to use the LiquidBiopsy system and immunofluorescence to test the human epidermal growth factor receptor 2 (HER2) status of CTCs in patients with breast cancer. MATERIALS AND METHODS: The LiquidBiopsy system was used to detect HER2-positive (HER2+) cells in whole blood by microfluidic immunomagnetic bead screening and immunofluorescence assay, according to the manufacturer;s instructions. HER2 expression on CTCs was assessed using the Ariol system, calibrated through spiking experiments of 100 cells (BT474, SKBR3, A431, and MDA-MB-231) and 2.5 × 107 white blood cells/mL from healthy donors. Seventy-one patients with breast cancer and 107 non-cancer donors consented to provide blood. RESULTS: Based on breast cancer cell lines experiments, HER2+ CTCs were defined as CTCs with HER2 immunofluorescence intensity ≥ 3.5 times higher than the CD45 immunofluorescence intensity (100% sensitivity and 99.9% specificity). Among the 71 patients with breast cancer, 31 (43.7%) had HER2+ tumor. Among the HER2+ patients, 41.9% (13/31) were found to be HER2+ based on CTC ≥ 1, and 25.8% (8/31) were positive based on CTC ≥ 3. In HER2-negative patients by pathologic examination, 1 (2.5%) patient was found to have ≥ 3 HER2+ CTCs, whereas 15 (37.5%) patients had ≥ 1 HER2+ CTC. HER2+ CTCs were detected at all stages, even in early breast cancer, but the detection rate was higher in metastatic breast cancer. CONCLUSION: This proof-of-concept study strongly suggests that HER2+ CTCs can be detected using the LiquidBiopsy system.
BACKGROUND: Most previous studies of circulating tumor cells (CTCs) are based on the CellSearch platform, but CellSearch has a number of limitations. This study aimed to use the LiquidBiopsy system and immunofluorescence to test the humanepidermal growth factor receptor 2 (HER2) status of CTCs in patients with breast cancer. MATERIALS AND METHODS: The LiquidBiopsy system was used to detect HER2-positive (HER2+) cells in whole blood by microfluidic immunomagnetic bead screening and immunofluorescence assay, according to the manufacturer;s instructions. HER2 expression on CTCs was assessed using the Ariol system, calibrated through spiking experiments of 100 cells (BT474, SKBR3, A431, and MDA-MB-231) and 2.5 × 107 white blood cells/mL from healthy donors. Seventy-one patients with breast cancer and 107 non-cancer donors consented to provide blood. RESULTS: Based on breast cancer cell lines experiments, HER2+ CTCs were defined as CTCs with HER2 immunofluorescence intensity ≥ 3.5 times higher than the CD45 immunofluorescence intensity (100% sensitivity and 99.9% specificity). Among the 71 patients with breast cancer, 31 (43.7%) had HER2+ tumor. Among the HER2+ patients, 41.9% (13/31) were found to be HER2+ based on CTC ≥ 1, and 25.8% (8/31) were positive based on CTC ≥ 3. In HER2-negative patients by pathologic examination, 1 (2.5%) patient was found to have ≥ 3 HER2+ CTCs, whereas 15 (37.5%) patients had ≥ 1 HER2+ CTC. HER2+ CTCs were detected at all stages, even in early breast cancer, but the detection rate was higher in metastatic breast cancer. CONCLUSION: This proof-of-concept study strongly suggests that HER2+ CTCs can be detected using the LiquidBiopsy system.
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