title: Pathological significance and prognostic role of microvessel density, evaluated using CD31, CD34, and CD105 in prostate cancer patients after radical prostatectomy with neoadjuvant therapy.
abstract: BACKGROUND
  Neoadjuvant hormonal therapy (NHT) is performed to improve the outcome in organ-confined prostate cancer. However, there is little information regarding the relationship between angiogenesis and NHT. The aim of this study was to identify a suitable method to evaluate the angiogenic status of tissue, and to determine the prognostic value of this method for biochemical recurrence in patients who had undergone radical prostatectomy after NHT.
  
  
  METHODS
  We analyzed 108 formalin-fixed specimens from patients treated by radical prostatectomy. NHT was administered in 48 patients (52.9%) and 60 patients who had a similar Gleason score and pT stage were selected as a non-NHT treated control group. Microvessel density (MVD) was measured using anti-CD31, anti-CD34, and anti-CD105 antibodies. The expressions of vascular endothelial growth factor (VEGF)-A and thrombospondin (TSP)-1 were also evaluated by immunohistochemistry. The prognostic value of CD31-, CD34-, and CD105-MVD for biochemical recurrence was investigated.
  
  
  RESULTS
  The mean/SD of CD105-MVD in the NHT group (13.3/4.7) was significantly (P < 0.001) lower than that in the non-NHT group (125.8/7.3). In the NHT group, CD105-MVD was associated with pT stage and it was positively correlated with VEGF-A expression (r = 0.56, P < 0.001) and negatively correlated with TSP-1 expression (r = 0.42, P = 0.003). CD105-MVD was identified as a significant predictor of biochemical recurrence (BCR) in patients treated with NHT (log rank test, P < 0.001). Although CD31- and CD34-MVD were significantly associated with pT stage or Gleason score in non-NHT group, they were not associated with pathological features and BCR in NHT group.
  
  
  CONCLUSIONS
  Our results indicate that CD105-MVD reflects the angiogenic conditions in prostate cancer tissues treated with NHT. CD105-MVD was also identified as a significant and independent predictor of biochemical recurrence in prostate cancer patients who underwent radical prostatectomy with NHT.
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.forename: Kensuke
authors.initials: K
authors.lastname: Mitsunari
authors.forename: Akihiro
authors.initials: A
authors.lastname: Asai
authors.forename: Kosuke
authors.initials: K
authors.lastname: Takehara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071063:Endoglin; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000628:therapy; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis; biochemical recurrence; neoadjuvant therapy; thrombospondin-1; vascular endothelial growth factor-A