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Change of Thrombospondin-1 Expression and Its Pathological Significance by Hormonal Therapy in Human Prostate Cancer Tissues Introduction and Objectives: Thrombospondin (TSP)-1 has been reported to play as inhibitory role in angiogenesis and cancer cell progression in various malignancies. However, its oncogenic activity and pathological roles in prostate cancer is controversial. In addition, detailed relationship between TSP-1 expression and androgen deprivation in human prostate cancer tissues is not still fully understood. The goal of this study is to examine whether TSP-1 expression is increased by hormonal therapy in patients with non-metastatic prostate cancer. Materials and Methods: One hundred and six patients who had undergone radical prostatectomy were examined retrospectively and divided into neo-adjuvant hormonal therapy (NHT) group (n = 52) and nonNHT group (n = 54). All patients showed no metastasis by various imaging examinations before surgery. We examined the TSP-1 expression and microvessel density (MVD, measured by using CD34 antibody) by immunohistochemical techniques. Relationships between TSP-1 expression and pathological features were investigated in non-NHT specimens. In addition, we compared TSP-1 expression and relationship between its expression and MVD in NHT group with those with non-NHT group. Results: Among 54 specimens with non-NHT, TSP-1 immunoreactivity was detected in only 9 (16.7%). In these patients, it was not associated with pT stage (p=0.620) and Gleason’s score (p=0.333). On the other hand, its positive ratio in NHT group (21/52, 40.4%) was significantly (p<0.001) higher than that in non-NHT one. In NHT group, mean and SD of MVD in TSP-1-positive-specimen (25.5 and 6.0 /high power field, HPF) was significantly lower (p=0.036) than it in negative-specimen (29.4 and 6.3 /HPF). However, such significant correlation was not detected in non-NHT group (p=0.274). Conclusion: Our data suggest that TSP-1 plays minimal roles for malignant aggressive including angiogenesis in prostate cancer tissues. However, its expression was up-regulated by hormonal therapy and its expression was significantly associated with MVD in specimens treated with hormonal therapy. From these results, TSP-1 is speculated to be useful as therapeutic target and tool of newly treatment strategy to inhibit cancer cell progression by combined with hormonal therapy in prostate cancer patients. .