title: Relationship Between Hematogenous Tumor Cell Dissemination and Cellular Immunity in DCIS Patients.
abstract: OBJECTIVE
  By definition, tumor cells do not pass the epithelial basement membrane in pre-invasive lesions. However, recently, it was shown that hematogenous tumor cell dissemination already takes place in patients with ductal carcinoma in situ (DCIS), giving disseminated tumor cells (DTCs) in the bone marrow the opportunity to interact with the peripheral immune system. We, therefore, investigated the relationship between DTCs and the peripheral innate and adaptive immune system of DCIS patients, as immunosurveillance might also be impaired in pre-invasive lesions.
  
  
  METHODS
  We analyzed the peripheral immune status of 115 DCIS patients by flow cytometry. Results were correlated with presence of DTCs, that were detected in the bone marrow by immunocytochemistry (pan-cytokeratin antibody A45-B/B3) using the automated cellular imaging system (ACIS) according to the international society of hematotherapy and graft engineering (ISHAGE) evaluation criteria. Apoptotic DTCs were characterized by positive M30 staining and cytomorphological criteria.
  
  
  RESULTS
  In contrast to breast cancer, we found no significant correlation between appearance of DTCs and quantitative distribution of T-cell sub-populations, B and NK-cells neither in the bone marrow nor in the peripheral blood. Moreover, DTCs did not affect the expression of important immunomodulatory antigens for functional integrity of specific immune response such as, TCR-ζ, CD28 or CD95. Interestingly, 39% of DTCs were positive for M30 expression and showed cytomorphological signs of apoptosis.
  
  
  CONCLUSIONS
  In contrast to breast cancer, DTCs of DCIS seem to be less immunogenic, which might result in a diverging way to evade immunosurveillance.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany ines.gruber@med.uni-tuebingen.de.
authors.forename: Ines V
authors.initials: IV
authors.lastname: Gruber
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Hartkopf
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Florin-Andrei
authors.initials: FA
authors.lastname: Taran
authors.affiliation: Department of Pathology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Sara Y
authors.initials: SY
authors.lastname: Brucker
authors.affiliation: HELIOS Clinic Berlin-Buch, Department of Gynecology and Obstetrics, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hanke
authors.affiliation: Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007157:Immunologic Surveillance; D053538:Keratin-18 / Q000032:analysis; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D009360:Neoplastic Cells, Circulating / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain
keywords: Ductal carcinoma in situ; apoptosis; breast cancer; disseminated tumor cell; immunosurveillance; tumor cell dormancy; tumor escape