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

Angiogenesis plays important roles in tumor growth and cancer cell dissemination in almost all cancers. In prostate cancer, there is general agreement that increased angiogenesis is an important factor in determining tumor development and prognosis in these patients. Microvessel density is recognized as a useful marker for evaluating the angiogenic status of cancer tissues. Many investigators have reported that microvessel density is significantly associated with pathological features and outcomes in prostate cancer patients; however, some researchers have expressed opposing opinions. As the reason for such discrepancy, previous reports have suggested differences in the methodologies of measuring microvessel density in cancer tissues. In the present review, we focus on the variation in such methods, including the selected area and the method used for (semi)quantification. In particular, we discuss the relationship between malignancy potential, tumor progression, and survival and differences in the antibodies used for detection of endothelial cells in detail. We briefly compare the pathological significance and prognostic roles of microvessel density measured using von Willebrand factor, CD31, CD34, and CD105. Based on these analyses, the advantages and limitations of microvessel density measurements in prostate cancer tissues are clarified. Improved "real" and "specific" markers of cancer-related angiogenesis are necessary for better predictions of prognoses and for discussion of treatment strategies for patients with prostate cancer. However, establishment of a satisfactory cancer-related endothelial marker could take a long time. Therefore, knowledge regarding the pathological significance of microvessel density - based on understanding of the advantages and limitations of microvessel density determination methods - is important.