Two-dimensional neovascular complexity is significantly higher in nontumor prostate tissue than in low-risk prostate cancer

Abstract

PurposeProstate cancer is the most frequent cancer in men in Europe. A major focus in urology is the identification of new biomarkers with improved accuracy in patients with low-risk prostate cancer. Here, we evaluated two-dimensional neovascular complexity in prostate tumor and nontumor biopsy cores by use of a computer-aided image analysis system and assessed the correlations between the results and selected clinical and pathological parameters of prostate carcinoma.Materials and MethodsA total of 280 prostate biopsy sections from a homogeneous series of 70 patients with low-risk prostate cancer (Gleason score 3+3, prostate-specific antigen [PSA]<10 ng/mL, and clinical stage T1c) who underwent systematic biopsy sampling and subsequent radical prostatectomy were analyzed. For each biopsy, 2-µm sections were treated with CD34 antibodies and were digitized by using an image analysis system that automatically estimates the surface fractal dimension.ResultsOur results showed that biopsy sections without cancer were significantly more vascularized than were tumors. No correlations were found between the vascular surface fractal dimension and patient's age, PSA and free-to-total PSA ratios, pathological stage, Gleason score, tumor volume, vascular invasion, capsular penetration, surgical margins, and biochemical recurrence.ConclusionsThe value of angiogenesis in prostate cancer is still controversial. Our findings suggest that low-risk prostate cancer tissues are less vascularized than are nontumor tissues. Further studies are necessary to understand whether angiogenesis is a hallmark of intermediate- and high-risk prostate cancer.

Targeting Angiogenesis in Prostate Cancer

“…Reasons for these conflicting results potentially include different counting methods, diferences in antibodies used, different population sizes, personal experience and pathological background [45]. A further limiting factor is the complex geometrical structure of the newly fromed vascular system, which is difficult to analyse on a two dimensional histological section [46]. Fractal geometry to estimate the surface dimension, computer aided automated image analysis, 3D models or magnetic resonance imaging could potentially be used to overcome these shortcomings, [46,47].…”

Response to Re: Reconsideration of the clinical and histopathological significance of angiogenesis in prostate cancer: Usefulness and limitations of microvessel density measurement

“…In recent years, they have reported that 2-D geometrical complexity in non-tumoral prostate tissues is significantly higher than that in low-risk prostate cancer. 4 This finding is worthy of attention to discuss the appropriate method in evaluation of angiogenic status in tissues. However, although they established the quantitative evaluation by using anti-CD31 antibody in 2005, 3 the relationships between vascular surface fractal dimension and clinicopathological features in prostate cancer tissues were analyzed by using anti-CD34 antibody.…”

“…However, although they established the quantitative evaluation by using anti-CD31 antibody in 2005, 3 the relationships between vascular surface fractal dimension and clinicopathological features in prostate cancer tissues were analyzed by using anti-CD34 antibody. 4 We previously reported that anti-CD31 and anti-CD34 have different characteristics to reflect the angiogenic status in human tissues of cancers, including prostate cancer. 5,6 Thus, even if new evaluation tools are developed, the uniformity of methods to detect cancer-related neovascularity is a problem that we still have to face.…”

“…This parameter depends on the number of vessels and pattern of distribution. In recent years, they have reported that 2‐D geometrical complexity in non‐tumoral prostate tissues is significantly higher than that in low‐risk prostate cancer . This finding is worthy of attention to discuss the appropriate method in evaluation of angiogenic status in tissues.…”

“…This finding is worthy of attention to discuss the appropriate method in evaluation of angiogenic status in tissues. However, although they established the quantitative evaluation by using anti‐CD31 antibody in 2005, the relationships between vascular surface fractal dimension and clinicopathological features in prostate cancer tissues were analyzed by using anti‐CD34 antibody . We previously reported that anti‐CD31 and anti‐CD34 have different characteristics to reflect the angiogenic status in human tissues of cancers, including prostate cancer .…”