title: Increased mobilisation of circulating endothelial progenitors in von Hippel-Lindau disease and renal cell carcinoma.
abstract: BACKGROUND
  Circulating endothelial cells (CECs) are a candidate biomarker for monitoring angiogenesis in cancer. Circulating endothelial cell subsets are mobilised by angiogenic mediators. Because of the highly angiogenic phenotype of renal cell carcinoma (RCC), we sought to assess the potential of CECs as a marker of RCC in patients with von Hippel-Lindau (VHL) disease and those with sporadic RCC.
  
  
  METHODS
  We performed multicolour flow cytometry to enumerate CECs in patients with RCC, patients with VHL disease with and without RCC, and normal subjects. Two subsets of CECs were evaluated: mature CECs (mCECs) and circulating endothelial progenitors (CEPs).
  
  
  RESULTS
  In patients with VHL disease and RCC and those with sporadic RCC (N=10), CEPs and the CEP:mCEC ratio were higher than in normal subjects (N=17) (median CEPs: 0.97 vs 0.19 cells μl(-1), respectively, P<0.01; median CEP:mCEC: 0.92 vs 0.58, respectively, P=0.04). However, in patients with VHL without RCC, CECs were not increased. In paired pre- and post-nephrectomy RCC patient samples (N=20), CEPs decreased after surgery (median difference 0.02 cells μl(-1), -0.06 to 1.2; P=0.05).
  
  
  CONCLUSIONS
  Circulating endothelial progenitors were elevated in RCC, but not in patients with VHL without RCC. Circulating endothelial progenitor enumeration merits further investigation as a monitoring strategy for patients with VHL.
authors.affiliation: Division of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, 375 Longwood Avenue, MASCO 426, Boston, MA 02215, USA. rbhatt@bidmc.harvard.edu
authors.forename: R S
authors.initials: RS
authors.lastname: Bhatt
authors.forename: A J
authors.initials: AJ
authors.lastname: Zurita
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.forename: A
authors.initials: A
authors.lastname: Norden-Zfoni
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: H K
authors.initials: HK
authors.lastname: Wu
authors.forename: P Y
authors.initials: PY
authors.lastname: Wen
authors.forename: D
authors.initials: D
authors.lastname: George
authors.forename: V P
authors.initials: VP
authors.lastname: Sukhatme
authors.forename: M B
authors.initials: MB
authors.lastname: Atkins
authors.forename: J V
authors.initials: JV
authors.lastname: Heymach
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000473:pathology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015996:Survival Rate; D016896:Treatment Outcome; D006623:von Hippel-Lindau Disease / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor