Prospective study of prostate tumor angiogenesis and cancer-specific mortality in the health professionals follow-up study.
OBJECTIVE
Tumor growth requires the development of independent vascular networks that are often primitive in morphology and function. We examined whether microvessel morphology contributes to the considerable biologic heterogeneity of prostate cancer.


METHODS
We evaluated microvessel morphology as a predictor of prostate cancer mortality among 572 men in the Health Professionals Follow-Up Study diagnosed with cancer during 1986 to 2000. We immunostained prostatectomy tumor block sections for endothelial marker CD34 and assessed microvessel density, vessel size (area and diameter), and irregularity of vessel lumen using image analysis. Proportional hazards models were used to assess microvessel density and morphology in relation to lethal prostate cancer.


RESULTS
Poorly differentiated tumors exhibited greater microvessel density, greater irregularity of the vessel lumen, and smaller vessels. During 20 years of follow-up, 44 men developed bone metastases or died of cancer. Men with tumors exhibiting the smallest vessel diameter, based on quartiles, were 6.0 times more likely (95% CI, 1.8 to 20.0) to develop lethal prostate cancer. Men with the most irregularly shaped vessels were 17.1 times more likely (95% CI, 2.3 to 128) to develop lethal disease. Adjusting for Gleason grade and prostate-specific antigen levels did not qualitatively change the results. Microvessel density was not linked to cancer-specific mortality after adjusting for clinical factors.


CONCLUSIONS
Aggressive tumors form vessels that are primitive in morphology and function, with consequences for metastases. Vascular size and irregularity reflect the angiogenic potential of prostate cancer and may serve as biomarkers to predict prostate cancer mortality several years after diagnosis.
Mucci
Lorelei A
LA
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. lmucci@hsph.harvard.edu
Powolny
Anna
A
Giovannucci
Edward
E
Liao
Zhiming
Z
Kenfield
Stacey A
SA
Shen
Rulong
R
Stampfer
Meir J
MJ
Clinton
Steven K
SK
D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D016001:Confidence Intervals; D005500:Follow-Up Studies; D006281:Health Occupations; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000401:mortality*; D011237:Predictive Value of Tests; D011336:Probability; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods / Q000401:mortality; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors
D017430:Prostate-Specific Antigen