The Effect of Endocrine Therapy on Angiogenesis and the Expression of Thrombospondin-1 and Vascular Endothelial Growth Factor in Prostate Cancer

Kwak, Cheol; Jeong, Hyeon; Byun, Seok Soo; Baek, Minki; Kim, Chul; Kim, Taehoon; Lee, Sang Eun

Abstract

PURPOSE
The exact role of angiogenesis in prostate cancer is unknown. We investigated whether endocrine therapy inhibits angiogenesis, and influences the expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, and vascular endothelial growth factor (VEGF) in prostate cancer.
MATERIALS AND METHODS
Employing immunohistochemistry, we assessed the expression of VEGF and TSP-1 in archival tissues from 46 patients with metastatic prostate cancer (30 before androgen deprivation therapy and 16 after at least 6-months' duration of androgen deprivation therapy). For each tumour, microvascular density (MVD) counts were determined using immunohistochemical staining for factor VIII. The relationship between MVD and the expression of VEGF and TSP-1, the tumour grade was assessed in metastatic prostate cancer.
RESULTS
The mean MVD counts (71.1 vessels per 200x high-power field) in 16 patients with metastatic cancer after androgen deprivation therapy was significantly higher than that (51.7) in 30 patients before androgen deprivation therapy (p<0.05). The immunohistochemical analysis demonstrated a higher TSP-1 expression (p<0.01), and a lower VEGF expression (p<0.01), in androgen deprivation group. There was no significant correlation between VEGF or TSP-1 expression and the mean MVD counts. The MVD counts had no correlation with Gleason scores or initial PSA levels.
CONCLUSIONS
Endocrine therapy in metastatic prostate cancer significantly decreased MVD counts, the expression of VEGF and significantly increased the expression of TSP-1. The present study shows that decreased angiogenesis including changes in the expressions of angiogenic factors, might have an important role in the therapeutic effect of androgen deprivation in metastatic prostate cancer.