Size-Based Isolation of Circulating Tumor Cells in Lung Cancer Patients Using a Microcavity Array System

Masahito Hosokawa, Hirotsugu Kenmotsu, Yasuhiro Koh, Tomoko Yoshino, Takayuki Yoshikawa, Tateaki Naito, Toshiaki Takahashi, Haruyasu Murakami, Yukiko Nakamura, Asuka Tsuya, Takehito Shukuya, Akira Ono, Hiroaki Akamatsu, Reiko Watanabe, Sachiyo Ono, Keita Mori, Hisashige Kanbara, Ken Yamaguchi, Tsuyoshi Tanaka, Tadashi MatsunagaNobuyuki Yamamoto

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Background:Epithelial cell adhesion molecule (EpCAM)-based enumeration of circulating tumor cells (CTC) has prognostic value in patients with solid tumors, such as advanced breast, colon, and prostate cancer. However, poor sensitivity has been reported for non-small cell lung cancer (NSCLC). To address this problem, we developed a microcavity array (MCA) system integrated with a miniaturized device for CTC isolation without relying on EpCAM expression. Here, we report the results of a clinical study on CTCs of advanced lung cancer patients in which we compared the MCA system with the CellSearch system, which employs the conventional EpCAM-based method.Methods:Paired peripheral blood samples were collected from 43 metastatic lung cancer patients to enumerate CTCs using the CellSearch system according to the manufacturer's protocol and the MCA system by immunolabeling and cytomorphological analysis. The presence of CTCs was assessed blindly and independently by both systems.Results:CTCs were detected in 17 of 22 NSCLC patients using the MCA system versus 7 of 22 patients using the CellSearch system. On the other hand, CTCs were detected in 20 of 21 small cell lung cancer (SCLC) patients using the MCA system versus 12 of 21 patients using the CellSearch system. Significantly more CTCs in NSCLC patients were detected by the MCA system (median 13, range 0-291 cells/7.5 mL) than by the CellSearch system (median 0, range 0-37 cells/7.5 ml) demonstrating statistical superiority (p = 0.0015). Statistical significance was not reached in SCLC though the trend favoring the MCA system over the CellSearch system was observed (p = 0.2888). The MCA system also isolated CTC clusters from patients who had been identified as CTC negative using the CellSearch system.Conclusions:The MCA system has a potential to isolate significantly more CTCs and CTC clusters in advanced lung cancer patients compared to the CellSearch system.

Original languageEnglish
Article numbere67466
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - 2013 Jun 28
Externally publishedYes

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Circulating Neoplastic Cells
Microcavities
lung neoplasms
Tumors
Lung Neoplasms
Cells
Cell Adhesion Molecules
cell adhesion
Non-Small Cell Lung Carcinoma
cells
epithelial cells
Small Cell Lung Carcinoma
neoplasm cells
Cell Separation
prostatic neoplasms
colorectal neoplasms
breast neoplasms
Colonic Neoplasms
Blood
clinical trials

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hosokawa, M., Kenmotsu, H., Koh, Y., Yoshino, T., Yoshikawa, T., Naito, T., ... Yamamoto, N. (2013). Size-Based Isolation of Circulating Tumor Cells in Lung Cancer Patients Using a Microcavity Array System. PLoS One, 8(6), [e67466]. https://doi.org/10.1371/journal.pone.0067466

Size-Based Isolation of Circulating Tumor Cells in Lung Cancer Patients Using a Microcavity Array System. / Hosokawa, Masahito; Kenmotsu, Hirotsugu; Koh, Yasuhiro; Yoshino, Tomoko; Yoshikawa, Takayuki; Naito, Tateaki; Takahashi, Toshiaki; Murakami, Haruyasu; Nakamura, Yukiko; Tsuya, Asuka; Shukuya, Takehito; Ono, Akira; Akamatsu, Hiroaki; Watanabe, Reiko; Ono, Sachiyo; Mori, Keita; Kanbara, Hisashige; Yamaguchi, Ken; Tanaka, Tsuyoshi; Matsunaga, Tadashi; Yamamoto, Nobuyuki.

In: PLoS One, Vol. 8, No. 6, e67466, 28.06.2013.

Research output: Contribution to journalArticle

Hosokawa, M, Kenmotsu, H, Koh, Y, Yoshino, T, Yoshikawa, T, Naito, T, Takahashi, T, Murakami, H, Nakamura, Y, Tsuya, A, Shukuya, T, Ono, A, Akamatsu, H, Watanabe, R, Ono, S, Mori, K, Kanbara, H, Yamaguchi, K, Tanaka, T, Matsunaga, T & Yamamoto, N 2013, 'Size-Based Isolation of Circulating Tumor Cells in Lung Cancer Patients Using a Microcavity Array System', PLoS One, vol. 8, no. 6, e67466. https://doi.org/10.1371/journal.pone.0067466
Hosokawa, Masahito ; Kenmotsu, Hirotsugu ; Koh, Yasuhiro ; Yoshino, Tomoko ; Yoshikawa, Takayuki ; Naito, Tateaki ; Takahashi, Toshiaki ; Murakami, Haruyasu ; Nakamura, Yukiko ; Tsuya, Asuka ; Shukuya, Takehito ; Ono, Akira ; Akamatsu, Hiroaki ; Watanabe, Reiko ; Ono, Sachiyo ; Mori, Keita ; Kanbara, Hisashige ; Yamaguchi, Ken ; Tanaka, Tsuyoshi ; Matsunaga, Tadashi ; Yamamoto, Nobuyuki. / Size-Based Isolation of Circulating Tumor Cells in Lung Cancer Patients Using a Microcavity Array System. In: PLoS One. 2013 ; Vol. 8, No. 6.
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AU - Hosokawa, Masahito

AU - Kenmotsu, Hirotsugu

AU - Koh, Yasuhiro

AU - Yoshino, Tomoko

AU - Yoshikawa, Takayuki

AU - Naito, Tateaki

AU - Takahashi, Toshiaki

AU - Murakami, Haruyasu

AU - Nakamura, Yukiko

AU - Tsuya, Asuka

AU - Shukuya, Takehito

AU - Ono, Akira

AU - Akamatsu, Hiroaki

AU - Watanabe, Reiko

AU - Ono, Sachiyo

AU - Mori, Keita

AU - Kanbara, Hisashige

AU - Yamaguchi, Ken

AU - Tanaka, Tsuyoshi

AU - Matsunaga, Tadashi

AU - Yamamoto, Nobuyuki

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N2 - Background:Epithelial cell adhesion molecule (EpCAM)-based enumeration of circulating tumor cells (CTC) has prognostic value in patients with solid tumors, such as advanced breast, colon, and prostate cancer. However, poor sensitivity has been reported for non-small cell lung cancer (NSCLC). To address this problem, we developed a microcavity array (MCA) system integrated with a miniaturized device for CTC isolation without relying on EpCAM expression. Here, we report the results of a clinical study on CTCs of advanced lung cancer patients in which we compared the MCA system with the CellSearch system, which employs the conventional EpCAM-based method.Methods:Paired peripheral blood samples were collected from 43 metastatic lung cancer patients to enumerate CTCs using the CellSearch system according to the manufacturer's protocol and the MCA system by immunolabeling and cytomorphological analysis. The presence of CTCs was assessed blindly and independently by both systems.Results:CTCs were detected in 17 of 22 NSCLC patients using the MCA system versus 7 of 22 patients using the CellSearch system. On the other hand, CTCs were detected in 20 of 21 small cell lung cancer (SCLC) patients using the MCA system versus 12 of 21 patients using the CellSearch system. Significantly more CTCs in NSCLC patients were detected by the MCA system (median 13, range 0-291 cells/7.5 mL) than by the CellSearch system (median 0, range 0-37 cells/7.5 ml) demonstrating statistical superiority (p = 0.0015). Statistical significance was not reached in SCLC though the trend favoring the MCA system over the CellSearch system was observed (p = 0.2888). The MCA system also isolated CTC clusters from patients who had been identified as CTC negative using the CellSearch system.Conclusions:The MCA system has a potential to isolate significantly more CTCs and CTC clusters in advanced lung cancer patients compared to the CellSearch system.

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