title: Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance.
abstract: OBJECTIVE
  The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting.
  
  
  METHODS
  From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975-1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295). The TMAs were stained for Ki67, endoglin and factor VIII-related antigen (vWf).
  
  
  RESULTS
  In univariate Cox analyses, increased Ki67 index, endoglin vascular density and vWf vascular density were associated with shorter cancer-specific survival. Ki67 index and endoglin vascular density added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours, high Ki67 index and high endoglin vascular density identified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65% cumulative risk of prostate cancer death). vWf vascular density in benign areas was a prognostic marker in GS 6 and 7 tumours.
  
  
  CONCLUSIONS
  Men with GS 6 tumours with both low Ki67 index and endoglin vascular density staining scores have a low risk of progression. Additional studies are needed to test whether these two markers can be applied to core biopsies to select patients suitable for surveillance.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Sweden. Andreas.Josefsson@medbio.umu.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Josefsson
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.forename: Torvald
authors.initials: T
authors.lastname: Granfors
authors.forename: Lars
authors.initials: L
authors.lastname: Karlberg
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000175:diagnosis* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D018450:Disease Progression; D000071063:Endoglin; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000401:mortality; D011956:Receptors, Cell Surface / Q000378:metabolism; D012307:Risk Factors; D046888:Tissue Array Analysis; D057832:Watchful Waiting / Q000706:statistics & numerical data; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D019394:Ki-67 Antigen; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; D017430:Prostate-Specific Antigen