title: Endothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells.
abstract: BACKGROUND
  Mature circulating endothelial cells (CEC) are surrogate markers of endothelial damage. CEC measured in patients with advanced cancer are thought not only to derive from damaged normal vasculature (n-CEC), but also from damaged (t-CEC). Therefore, assays that allow the discrimination between these two putative types of CEC are thought to improve the specificity of the enumeration of CEC in cancer.
  
  
  METHODS
  Identification of tumour-associated endothelial markers (TEM) by comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC in peripheral blood of cancer patients by incorporating TEM in our novel flow cytometry-based CEC detection assay.
  
  
  RESULTS
  No difference in antigen expression between normal and malignant endothelial cells (ECs) was found for CD54, CD109, CD137, CD141, CD144 and CXCR7. In contrast, overexpression for CD105, CD146, CD276 and CD309 was observed in tumour ECs compared with normal ECs. CD276 was most differentially expressed and chosen as a marker for further investigation. CD276-expressing CEC were significantly higher in 15 patients with advanced colorectal cancer (median 9 (range 1-293 cell per 4 ml); P<0.005), in 83 patients with a glioblastoma multiforme (median 10 (range 0-804); P<0.0001) and in 14 patients with advanced breast cancer (median 14 (range 0-390) P<0.05) as compared with 24 healthy individuals (median 3 (range 0-11)). Of all patients with malignancies, 58% had CD276(+) CEC counts above the ULN (8 cell per 4 ml).
  
  
  CONCLUSIONS
  The present study shows that CD276 can be used to discriminate ECs from malignant tissue from ECs from normal tissue. In addition, CD276(+) CEC do occur in higher frequencies in patients with advanced cancer.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kraan
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: van den Broek
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Verhoef
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Grunhagen
authors.affiliation: Department of Neuro-oncology, Erasmus MC Cancer Institute, box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Taal
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D060887:B7 Antigens / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D009369:Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology
chemical_list: D060887:B7 Antigens; D014408:Biomarkers, Tumor; C423237:CD276 protein, human