Thrombospondin-1, vascular endothelial growth factor expression and their relationship with p53 status in prostate cancer and benign prostatic hyperplasia.
OBJECTIVE
To evaluate the expression of thrombospondin-1 (TSP-1, a potent inhibitor of angiogenesis) and vascular endothelial growth factor (VEGF, an important angiogenic factor in solid tumours) in prostate cancer, and their relationship with p53 status.


METHODS
Using immunohistochemistry, the expression of VEGF, TSP-1 and p53 was assessed in 82 archival tissue specimens from 23 patients with benign prostatic hyperplasia (BPH), 22 with localized prostate cancer and 37 with metastatic prostate cancer. Seven of the last group had received androgen deprivation therapy. The relationship between the expression of VEGF, TSP-1 and p53 status was also evaluated with tumour grade and stage in patients with prostate cancer.


RESULTS
The seven patients receiving hormonal treatment were excluded from the analysis because androgen deprivation significantly increased TSP-1 and decreased VEGF expression (both P < 0.01). Immunohistochemical analysis showed significantly higher VEGF and significantly lower TSP-1 expression (both P < 0.01) in prostate cancer than in BPH tissues. There was also significantly higher VEGF and significantly lower TSP-1 expression (both P < 0.05) in tissues from metastatic than localized prostate cancer. There was no significant correlation between VEGF or TSP-1 expression and Gleason score, but a significant inverse correlation between TSP-1 and VEGF expression. There was a significant association between VEGF expression and p53 status (P < 0.05), but TSP-1 expression was not associated with p53 status.


CONCLUSIONS
Angiogenic factors, including VEGF and TSP-1, might be important in the development and progression of prostate cancer. These changes seem to be influenced by p53 status. Identifying the angiogenic factors involved in prostate cancer might lead to the development of diagnostic or therapeutic strategies based on anti-angiogenesis.
Kwak
C
C
Department of Urology and Clinical Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Jin
R J
RJ
Lee
C
C
Park
M S
MS
Lee
S E
SE
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors