title: Individual profiling of circulating tumor cell composition and therapeutic outcome in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  Circulating tumor cells (CTCs) have been proposed as a monitoring tool in patients with solid tumors. So far, automated approaches are challenged by the cellular heterogeneity of CTC, especially the epithelial-mesenchymal transition. Recently, Yu and colleagues showed that shifts in these cell populations correlated with response and progression, respectively, to chemotherapy in patients with breast cancer. In this study, we assessed which non-hematopoietic cell types were identifiable in the peripheral blood of hepatocellular carcinoma (HCC) patients and whether their distribution during treatment courses is associated with clinical characteristics.
  
  
  METHODS
  Subsequent to few enrichment steps, cell suspensions were spun onto glass slides and further characterized using multi-immunofluorescence staining. All non-hematopoietic cells were counted and individual cell profiles were analyzed per patient and treatment.
  
  
  RESULTS
  We detected a remarkable variation of cells with epithelial, mesenchymal, liver-specific, and mixed characteristics and different size ranges. The distribution of these subgroups varied significantly between different patient groups and was associated with therapeutic outcome. Kaplan-Meier log-rank test showed that a change in the ratio of epithelial to mesenchymal cells was associated with longer median time to progression (1 vs 15 months; P = .03; hazard ratio = 0.18; 95% confidence interval = 0.01-2.75).
  
  
  CONCLUSIONS
  Our data suggest that different CTC populations are identifiable in peripheral blood of HCC patients and, for the first time in HCC, that these individual cell type profiles may have distinct clinical implications. The further characterization and analysis of patients in this ongoing study seems to be warranted.
authors.affiliation: Department of Medical Oncology, Molecular Oncology Risk-Profile Evaluation, West German Cancer Center, University Hospital of Essen, Essen, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Nel
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Judith
authors.initials: J
authors.lastname: Ertle
authors.forename: Frank
authors.initials: F
authors.lastname: Weber
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Andreas-Claudius
authors.initials: AC
authors.lastname: Hoffmann
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