title: Detection of circulating tumor cell subpopulations in patients with head and neck squamous cell carcinoma (HNSCC).
abstract: BACKGROUND
  Since image based diagnostic tools fail to detect early metastasis in head and neck squamous cell carcinoma (HNSCC) it is crucial to develop minimal invasive diagnostic methods. A promising approach is to identify and characterize circulating tumor cells (CTC) in the peripheral blood of HNSCC patients. In this pilot study, we assessed which non-hematopoietic cell types are identifiable and whether their numbers differ in pre- and postoperative blood samples.
  
  
  METHODS
  20 ml citrated peripheral blood was taken from 10 HNSCC patients before and after curative resection. CTC were enriched using density gradient centrifugation. CTC presence was verified by multi-immunofluorescence staining against cytokeratin (CK; epithelial), N-cadherin (mesenchymal); CD133 (stem-cell), CD45 (hematopoietic) and DAPI (nucleus). Individual cell type profiles were analyzed.
  
  
  RESULTS
  We were able to detect cells with epithelial properties like CK+/N-cadherin-/CD45- and CK+/CD133-/CD45- as well as cells with mesenchymal features such as N-cadherin+/CK-/CD45- and cells with both characteristics like N-cadherin+/CK+/CD45-. We also observed cells showing stem cell-like features like CD133+/CK-/CD45- and cells with both epithelial and stem cell-like features such as CD133+/CK+/CD45-. The number of CK positive cells (p = 0.002), N-cadherin positive cells (p = 0.002) and CD133 positive cells (p = 0.01) decreased significantly after resection. Kaplan-Meier test showed that the survival was significantly shorter when N-cadherin+ cells were present after resection (p = 0.04; 474 vs. 235 days; [HR] = 3.1).
  
  
  CONCLUSIONS
  This is - to the best of our knowledge- the first pilot study identifying different CTC populations in peripheral blood of HNSCC patients and showing that these individual cell type profiles may have distinct clinical implications.
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weller
authors.affiliation: Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Nel
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hassenkamp
authors.affiliation: Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gauler
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schlueter
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Otorhinolaryngology, Evangelisches Krankenhaus Duesseldorf, Duesseldorf, Germany.
authors.forename: Paulette
authors.initials: P
authors.lastname: Dountsop
authors.affiliation: Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
authors.forename: Andreas-Claudius
authors.initials: AC
authors.lastname: Hoffmann
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Department of Otorhinolaryngology, St. Anna-Klinik, Wuppertal, Germany.
authors.forename: Götz
authors.initials: G
authors.lastname: Lehnerdt
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D019070:Cell Lineage; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor