Re: Reconsideration of the clinical and histopathological significance of angiogenesis in prostate cancer: Usefulness and limitations of microvessel density measurement Although there are currently no biomarkers of net angiogenic activity in prostate cancer (PCa), microvessel density (MVD) represents the surrogate biomarker of angiogenesis, and has been shown to correlate with progression, and other upstream and downstream regulators of angiogenesis.1 Miyata and Sakai reviewed the relationships between MVD and clinicopathological features, progression and survival in patients with PCa.2 They paid attention to the reasons for the conflicting MVD results, such as differences in population size, the pathological background, the antibody used for detection endothelial cells, the counting method, personal experience and selection of the tumor area.2 However, MVD is substantially limited by the highly irregular geometry that the microvascular system assumes in "real space." Angiogenesis is a dynamic process that is discontinuous in "space" and "time." The main feature of the newly generated vasculature is the structural diversity of the vessel sizes, shapes and connecting patterns. At a basic level, the practice of histology involves looking at an image (visual perception) and interpreting what is seen (cognition), and experience gives a histologist the perceptual and cognitive skills to know what information to look for, and how to interpret that information on the basis of the accumulated information processed from previous encounters with similar images. What makes the task extremely difficult is the high degree of "geometrical variability," and histologists can never see all the possible variations no matter how long they practice or how many images they see. However, objective computer-aided descriptors of the vascular complexity can be abstracted from the fractal geometry. The vascular system can be geometrically depicted as a fractal network of vessels that irregularly branch with a systematic reduction in their length and diameter. Fractal objects are mainly characterized by four properties: (i) the irregularity of their shape; (ii) the "self-similarity" of their structure; (iii) their fractal dimension; and (iv) scaling, which means that the measured properties depends on the scale at which they are measured.3 In 2005, we introduced the surface fractal dimension, D s , as an index of twodimensional geometrical complexity of vascular network, and evaluated its behavior during computer-simulated changes in vessel density and distribution. 3 We showed that D s depends on: (i) the number of vessels; (ii) the spatial relationships between the vessels; and (iii) the interactions between the vessels and the surrounding environment.3 Recently, we investigated 280 prostate biopsy sections from a series of 70 patients with low-risk PCa (Gleason score 3 + 3, prostatespecific antigen <10 ng/mL) and clinical stage T1c using an image analysis system that automatically estimates the D s.
4Our results showed that biopsy sect...
