BACKGROUND AND AIMS: 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.
BACKGROUND AND AIMS: 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: Andreas-Claudius Hoffmann; Peter Wild; Christina Leicht; Simone Bertz; Kathleen D Danenberg; Peter V Danenberg; Robert Stöhr; Michael Stöckle; Jan Lehmann; Martin Schuler; Arndt Hartmann Journal: Neoplasia Date: 2010-08 Impact factor: 5.715
Authors: Ken A Olaussen; Ariane Dunant; Pierre Fouret; Elisabeth Brambilla; Fabrice André; Vincent Haddad; Estelle Taranchon; Martin Filipits; Robert Pirker; Helmut H Popper; Rolf Stahel; Laure Sabatier; Jean-Pierre Pignon; Thomas Tursz; Thierry Le Chevalier; Jean-Charles Soria Journal: N Engl J Med Date: 2006-09-07 Impact factor: 91.245
Authors: Matthew G Krebs; Jian-Mei Hou; Robert Sloane; Lee Lancashire; Lynsey Priest; Daisuke Nonaka; Tim H Ward; Alison Backen; Glen Clack; Andrew Hughes; Malcolm Ranson; Fiona H Blackhall; Caroline Dive Journal: J Thorac Oncol Date: 2012-02 Impact factor: 15.609
Authors: Andreas-Claudius Hoffmann; Ryutaro Mori; Daniel Vallbohmer; Jan Brabender; Ellen Klein; Uta Drebber; Stephan E Baldus; Janine Cooc; Mizutomo Azuma; Ralf Metzger; Arnulf H Hoelscher; Kathleen D Danenberg; Klaus L Prenzel; Peter V Danenberg Journal: Neoplasia Date: 2008-07 Impact factor: 5.715
Authors: Andreas-Claudius Hoffmann; Andreas-Claudius Hoffman; Kathleen D Danenberg; Helge Taubert; Peter V Danenberg; Peter Wuerl Journal: Clin Cancer Res Date: 2009-08-11 Impact factor: 12.531
Authors: Colin M Court; Shuang Hou; Paul Winograd; Nicholas H Segel; Qingyu Wilda Li; Yazhen Zhu; Saeed Sadeghi; Richard S Finn; Ekambaram Ganapathy; Min Song; Samuel W French; Bita V Naini; Shonan Sho; Fady M Kaldas; Ronald W Busuttil; James S Tomlinson; Hsian-Rong Tseng; Vatche G Agopian Journal: Liver Transpl Date: 2018-07 Impact factor: 5.799
Authors: Ivonne Nel; Paul David; Guido G H Gerken; Joerg F Schlaak; Andreas-Claudius Hoffmann Journal: Hepatol Int Date: 2014-06-03 Impact factor: 6.047