Prognostic Impact of Circulating Tumor Cell Detected Using a Novel Fluidic Cell Microarray Chip System in Patients with Breast Cancer
Takeshi Sawada,
Jungo Araki,
Toshinari Yamashita,
Manami Masubuchi,
Tsuneko Chiyoda,
Mayu Yunokawa,
Kumiko Hoshi,
Shoichi Tao,
Shohei Yamamura,
Shouki Yatsushiro,
Kaori Abe,
Masatoshi Kataoka,
Tatsu Shimoyama,
Yoshiharu Maeda,
Katsumasa Kuroi,
Kenji Tamura,
Tsuneo Sawazumi,
Hironobu Minami,
Yoshihiko Suda,
Fumiaki Koizumi
Affiliations
Takeshi Sawada
Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
Jungo Araki
Konica Minolta, Inc., 1 Sakuramachi, Hino, Tokyo 191-8511, Japan
Toshinari Yamashita
Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
Manami Masubuchi
Konica Minolta, Inc., 1 Sakuramachi, Hino, Tokyo 191-8511, Japan
Tsuneko Chiyoda
Konica Minolta, Inc., 1 Sakuramachi, Hino, Tokyo 191-8511, Japan
Mayu Yunokawa
Department of Breast Oncology and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Kumiko Hoshi
Konica Minolta, Inc., 1 Sakuramachi, Hino, Tokyo 191-8511, Japan
Shoichi Tao
Konica Minolta, Inc., 1 Sakuramachi, Hino, Tokyo 191-8511, Japan
Shohei Yamamura
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
Shouki Yatsushiro
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
Kaori Abe
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
Masatoshi Kataoka
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
Tatsu Shimoyama
Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
Yoshiharu Maeda
Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
Katsumasa Kuroi
Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
Kenji Tamura
Department of Breast Oncology and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Tsuneo Sawazumi
Konica Minolta, Inc., 1 Sakuramachi, Hino, Tokyo 191-8511, Japan
Hironobu Minami
Department of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
Yoshihiko Suda
Konica Minolta, Inc., 1 Sakuramachi, Hino, Tokyo 191-8511, Japan
Fumiaki Koizumi
Division of Clinical Research Support, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
Various types of circulating tumor cell (CTC) detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010) of MDA-MB-231 cells and an equivalent detection rate (p = 0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC+ and CTC− was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p = 0.01591); in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p = 0.000244). CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.
