title: A novel approach using telomerase-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients.
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.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Akinori
authors.initials: A
authors.lastname: Masago
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Akazawa
authors.forename: Fumine
authors.initials: F
authors.lastname: Tsukamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ozawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Tsujino
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011960:Receptors, Estrogen / Q000378:metabolism; D012016:Reference Values; D019098:Telomerase; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D019098:Telomerase