Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study

Abstract

A B S T R A C T PurposeTumor 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. MethodsWe 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. ResultsPoorly 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. ConclusionAggressive 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.

High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy

“…Increased MVD has also been described as a negative prognostic factor in solid tumors but has not been explored in DLBCL treated with R-CT. 13 The prognostic value of the MVD in our study agrees with previously published GEP data on DLBCL. 2 The gene expression signatures 'stromal 1' and 'stromal 2', related to extracellular matrix and angiogenesis-related genes, respectively, were synergistic in predicting survival.…”

Diabetes Mellitus and Prostate Cancer Risk; A Nationwide Case–Control Study within PCBaSe Sweden

“…The influence of metabolic factors may further need a relatively well-differentiated target tissue for their action. T2DM and long-term hyperglycemia frequently results in microvascular complications due to capillary dysfunction and altered shape and size of intraprostatic microvessels have been linked to the risk of lethal prostate cancer (39). Decreased microcirculation might thus alternatively explain the reduced risk among men with T2DM (40).…”

Growth Inhibition and Apoptosis Induction of Human Umbilical Vein Endothelial Cells by Apogossypolone

“…And it has been reported that microvessel density, a measurement of prostate cancer angiogenesis, has been shown to be a predictor of metastasis and survival (Weidner et al, 1993). It is shown that that the microvessel density in prostate cancer tissues is significantly higher than normal prostate, and the microvessel density in metastatic prostate cancer is higher than that in nonmetastatic cancer (Brawer et al, 1994;Mucci et al, 2009;Aragon-Ching et al, 2010). Thus, targeting angiogenesis has been the subject of several clinical investigations.…”