support the opinion that newly developed blood vessels in cancer tissues play important roles in cancer cell survival and tumor growth though supply of oxygen and nutrition. In addition, such neovasculature can also enable cancer cell dissemination from the primary tumor to distant organs. Therefore, it is possible that evaluation of angiogenesis in the primary tumor mass is a useful marker for diagnosis of disease stage, metastasis and outcome in patients with solid tumors. However, it is still unclear whether existing evaluation methods for cancer tissues can exactly reflect the status and pathological roles of angiogenesis.In a previous review, we emphasized that the pathological significance and prognostic value of MVD in patients with prostate cancer is unclear because of differences in methodology, including antibodies used, counting method and selection of area.2 Conversely, Taverna et al. showed the influence of the structural diversity of the cancer-related vasculature on the evaluation of the significance and role of angiogenesis in cancer tissues.1 Briefly, neovasculatures in cancer tissues show diversity in vessel sizes, shapes and connecting patterns, because they have complex forms of branched anatomical structure. Additionally, the process of angiogenesis comprises various steps, such as proliferation, migration and tube formation. Therefore, they suggested surface fractal dimension, as a numerical index of the 2-D geometrical complexity of tumor vascular networks, to enable evaluation in the quantitative method.3 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. 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. 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.We agree with the opinion that it is still unclear which method most accurately reflects the pathological roles and clinical significance of angiogenesis in patients with prostate cancer. In addition, another open question is regarding the standardization of measuring method. Regardless of the numerous investigators who have reported on the relationships between MVD and clinicopathological features, tumor progression, and survival cancers, there is no study wherein MVD is used as a criterion for selection of enrolled patients, and strategies of o...
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