title: Increased microvascular proliferation is negatively correlated to tumour blood flow and is associated with unfavourable outcome in endometrial carcinomas.
abstract: BACKGROUND
  We aimed to study the angiogenic profile based on histomorphological markers in endometrial carcinomas in relation to imaging parameters obtained from preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) and to explore the potential value of these markers to identify patients with poor outcome.
  
  
  METHODS
  In fifty-four surgically staged endometrial carcinoma patients, immunohistochemical staining with factor VIII and Ki67 allowed assessment of microvessel density (MVD) and microvascular proliferation reflecting tumour angiogenesis. In the same patients, preoperative pelvic DCE-MRI and DWI allowed the calculation of parameters describing tumour microvasculature and microstructure in vivo.
  
  
  RESULTS
  Microvascular proliferation was negatively correlated to tumour blood flow (Fb) (r=-0.36, P=0.008), capillary permeability surface area product (PS) (r=-0.39, P=0.004) and transfer from the blood to extravascular extracellular space (EES) (Ktrans) (r=-0.40, P=0.003), and was positively correlated to tumour volume (r=0.34; P=0.004). High-tumour microvascular proliferation, low Fb and low Ktrans were all significantly associated with reduced progression/recurrence-free survival (P<0.05).
  
  
  CONCLUSIONS
  Disorganised angiogenesis with coexisting microvascular proliferation and low tumour blood flow is a poor prognostic factor supporting that hypoxia is associated with progression and metastatic spread in endometrial carcinomas.
authors.affiliation: 1] Department of Radiology, Haukeland University Hospital, Jonas Liesvei 65, Postbox 7800, 5021 Bergen, Norway [2] Section for Radiology, Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway.
authors.forename: I S
authors.initials: IS
authors.lastname: Haldorsen
authors.affiliation: 1] Centre for Cancer Biomarkers, The Gade Institute, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway [2] Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Stefansson
authors.affiliation: 1] Department of Radiology, Haukeland University Hospital, Jonas Liesvei 65, Postbox 7800, 5021 Bergen, Norway [2] Department of Physics and Technology, University of Bergen, 5020 Bergen, Norway.
authors.forename: R
authors.initials: R
authors.lastname: Grüner
authors.affiliation: 1] Department of Radiology, Haukeland University Hospital, Jonas Liesvei 65, Postbox 7800, 5021 Bergen, Norway [2] Section for Radiology, Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway.
authors.forename: J A
authors.initials: JA
authors.lastname: Husby
authors.affiliation: Department of Radiology, Haukeland University Hospital, Jonas Liesvei 65, Postbox 7800, 5021 Bergen, Norway.
authors.forename: I J
authors.initials: IJ
authors.lastname: Magnussen
authors.affiliation: 1] Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
authors.forename: H M J
authors.initials: HM
authors.lastname: Werner
authors.affiliation: Unit for applied Clinical Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Postbox 8905, 7491 Trondheim, Norway.
authors.forename: Ø O
authors.initials: ØO
authors.lastname: Salvesen
authors.affiliation: 1] Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Bjørge
authors.affiliation: 1] Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Trovik
authors.affiliation: 1] Department of Radiology, Haukeland University Hospital, Jonas Liesvei 65, Postbox 7800, 5021 Bergen, Norway [2] Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Taxt
authors.affiliation: 1] Centre for Cancer Biomarkers, The Gade Institute, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway [2] Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: L A
authors.initials: LA
authors.lastname: Akslen
authors.affiliation: 1] Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
authors.forename: H B
authors.initials: HB
authors.lastname: Salvesen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology; D011446:Prospective Studies