title: Vascular morphology differentiates prostate cancer mortality risk among men with higher Gleason grade.
abstract: Higher Gleason grade is associated with prostate cancer mortality; however, there is significant heterogeneity in this association. We evaluated whether vessel morphology, a biomarker of angiogenesis, aided in distinguishing mortality risks among men with high Gleason grading.
  
  
  
  We characterized vessel morphology (area and irregularity) among 511 patients diagnosed with prostate cancer during 1986 to 2000, re-reviewed Gleason grade, and followed men through 2012. Men were grouped according to integrated vessel lumen irregularity and vessel area across Gleason grade. The more angiogenic group was identified as those with more irregular vessel lumen and smaller vessel area. Crude rates (95 % confidence intervals) and survival probability were estimated across Gleason grade and vessel morphology.
  
  
  
  During a median 14-year follow-up, 62 men developed bone metastases or died of prostate cancer. Lethality rates were uniformly low within Gleason grade categories 6 and 7(3 + 4), regardless of vessel morphology. However, among men with Gleason grades of 7(4 + 3) or 8-10, the more angiogenic group was associated with fourfold higher risk of lethal outcomes compared to those with less angiogenic potential. Ten-year survival probability ranged from 95 to 74 % according to the extent of vessel morphology (p < 0.0001, log-rank test).
  
  
  
  Vessel morphology may aid Gleason grading in predicting prostate cancer mortality risks among men diagnosed with high-grade Gleason cancers.
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. meyang@hsph.harvard.edu.
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Zu
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Rider
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.|Pathology Unit, Addarii Institut, S.Orsola-Malpighi Hospital, 40138, Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: The Division of Medical Oncology, The Department of Internal Medicine, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA.|Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D011467:Prostate / Q000098:blood supply*; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology; D012306:Risk
chemical_list: D017430:Prostate-Specific Antigen
keywords: Angiogenesis; Gleason grade; Prostate cancer mortality; Vessel morphology