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A novel approach using telomerase-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients

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Abstract

The aim of this study was to develop a new method for detecting circulating tumor cells (CTCs) in breast cancer patients by using the telomerase-specific replication-selective adenovirus OBP-401. Once transfected, OBP-401 can replicate only in telomerase expressing cells and emit fluorescence as it replicates so that the transfected cells become easily recognizable. Peripheral blood samples were drawn from 50 metastatic breast cancer patients and 27 early breast cancer patients. Blood samples were subjected to both the OBP-401 and CellSearch assays for the detection of CTCs and the results were compared. The recovery rate of the OBP-401 assay was one CTC in 7.5 ml blood combined with high specificity since no CTC was observed in 80 healthy controls. In 50 metastatic patients, 21 patients (42%) were identified as positive with the OBP-401 assay and 27 patients (54%) with the CellSearch assay. The CellSearch assay showed a significantly higher positivity for hormone receptor (HR)-positive tumors (estrogen receptor and/or progesterone receptor-positive tumors) (61%, 25/41, P = 0.012) or CA15-3-positive tumors (69%, 24/35, P = 0.003) than for HR-negative tumors (13%, 1/8) or CA15-3-negative tumors (21%, 3/14), respectively. Contrary, the OBP-401 assay results were similar regardless of their HR status (positive: 44% vs. negative: 38%, P = 0.738) or CA15-3 positivity (positive: 40% vs. negative: 50%, P = 0.523). Of the 27 early stage patients, four patients (15%) were identified by the OBP-401 assay and by the CellSearch assay, respectively, but there was no overlap in the CTCs-positive patients. In conclusion, the OBP-401 assay is comparable to the CellSearch assay in the detection rate of CTCs in both metastatic and early breast cancer patients. However, there was a great discrepancy in patients with CTCs between both assays. The OBP-401 assay may isolate CTCs with other biological characteristics which CTCs detected by the CellSearch assay do not have.

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Acknowledgments

We thank Drs N. Maruyama, T. Tanei, M. Okishiro, S. Michishita, M. Nishio, and R. Fukushima for their help for obtaining informed consents and collecting blood samples, and also all patients who participated in this study. This study was supported by the Research grant from Sysmex Corp. (J070701315 to S.N.).

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, 2-2-E-10 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Seung Jin Kim, Yasuhiro Tamaki & Shinzaburo Noguchi

  2. Research Division, Central Research Laboratories, Sysmex Corporation, 4-4-4 Takatsukadai, Nishi-ku, Kobe, Hyogo, 651-2271, Japan

    Akinori Masago, Jun Sato, Toshiyuki Ozawa & Yukio Tsujino

  3. Department of Breast and Endocrine Surgery, Osaka Koseinenkin Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka, Osaka, 553-0003, Japan

    Kenji Akazawa & Fumine Tsukamoto

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  1. Seung Jin Kim
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  2. Akinori Masago
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  3. Yasuhiro Tamaki
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  4. Kenji Akazawa
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  7. Toshiyuki Ozawa
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  9. Shinzaburo Noguchi
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Correspondence to Shinzaburo Noguchi.

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Kim, S.J., Masago, A., Tamaki, Y. et al. A novel approach using telomerase-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients. Breast Cancer Res Treat 128, 765–773 (2011). https://doi.org/10.1007/s10549-011-1603-2

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  • DOI: https://doi.org/10.1007/s10549-011-1603-2

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