title: Size-based isolation of circulating tumor cells in lung cancer patients using a microcavity array system.
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.
authors.affiliation: Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshino
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Asuka
authors.initials: A
authors.lastname: Tsuya
authors.forename: Takehito
authors.initials: T
authors.lastname: Shukuya
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Akamatsu
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Ono
authors.forename: Keita
authors.initials: K
authors.lastname: Mori
authors.forename: Hisashige
authors.initials: H
authors.lastname: Kanbara
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule