Vascular endothelial growth factor and its correlation with angiogenesis and p53 expression in prostate cancer

BACKGROUND. Previously it was demonstrated that in prostate tumors, angioge nesis measured as microvessel density (MVD) is associated with tumor stage as well as WHO grade and is an independent predictor of clinical outcome. V ascular endothelial growth factor (VEGF) is a major inducer of angiogenesis . There is some evidence that P53 mutations cause overexpression of VEGF. W e studied VEGF expression, p53 overexpression, and P53 mutations in prostat e cancer (PCA) to investigate the role of VEGF as an angiogenic marker and the possible deregulation of VEGF as a result of P53 mutations in PCA. METHODS. Immunohistochemical staining with a polyclonal VEGF antibody was p erformed in 55 paraffin-embedded PCA, in which MVD had previously been dete rmined, as well as in 5 prostatic adenomas (PA) and 20 adjacent normal pros tate tissues. Ln addition, 37 PCA and 5 PAs were examined for p53 expressio n by immunohistochemistry. Temperature gradient gel electrophoresis (TGGE) was performed in 13 of these PCA to screen for P53 mutations. VEGF expressi on, p53 expression, and mutations were then correlated with tumor stage, gr ade, MVD, and clinical outcome. RESULTS. While PA and normal prostate tissue generally showed no or only lo w VEGF expression, there was a significant increase in VEGF expression with tumor stage, grade, and MVD in PCA. During clinical follow-up (mean, 31.9 months), 9 of 55 patients had tumor progression. Significant differences in VEGF expression were found between patients with tumor progression and tho se without (P = 0.0004). Of the 37 PCA evaluated for p53 expression, 12 exh ibited p53 overexpression. TGGE revealed P53 mutations in 3 of 13 PCA. Howe ver, there was no correlation between VEGF expression, p53 overexpression, and P53 mutation, respectively. CONCLUSIONS. VEGF seems to be an important, clinically relevant inducer of angiogenesis in PCA. VEGF expression was shown to correlate positively with tumor stage, grade, MVD, and clinical outcome. However, regulation of VEGF in PCA appears to be independent of p53 expression. Prostate 45:216-224, 2 000. (C) 2000 Wiley-Liss, Inc.