The relation of p53 protein nuclear accumulation and angiogenesis in human prostatic carcinoma

Abstract

All neoplasms require angiogenesis and resulting neovascularity for growth beyond 1 mm 2 . Quantitative microvessel density (MVD) has been shown to provide staging and prognostic signi®cance in human prostate cancer (CaP). recently, it has been demonstrated that loss of the wild-type allele of the p53 tumour suppressor gene results in reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. There is also an increased expression of vascular endothelial growth factor which promotes neovascularization. p53 gene mutation and MVD were investigated in men with prostate cancer. Sections from 103 radical prostatectomy cases were evaluated with immunohistochemistry to detect mutant p53 proteins. Quantitative MVD was performed on the cases exhibiting p53 positive staining and compared with negative ®elds of similar Gleason grade on the same histologic sections.Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei. In 19 of these 20 cases, the MVD in p53 positive areas was greater than corresponding control regions (overall P`0.0001). Extent of p53 abnormality, as well as MVD, correlated with pathologic stage.These data suggest that mutations of the p53 tumour suppressor gene may be associated with increased angiogenesis in CaP. In addition to providing staging and prognostic information, this relationship potentially has therapeutic implications.

p53 immunoexpression in stepwise progression of cutaneous squamous cell carcinoma and correlation with angiogenesis and cellular proliferation

“…Such categorization could make the relationship between p53 and angiogenesis disappear, even with the neoangiogenesis marker. However, some of them demonstrated a positive correlation [46][47][48][49][50][51][52], indicating that this issue must be further investigated.…”

“…Using panendothelial markers, MVD significantly correlates with p53 positivity in prostatic [46], breast [47] and gastrointestinal cancer [48][49][50][51][52]. However such correlation has not been found in gallbladder [53] and hepatocellular carcinoma [54].…”

Inhibition of tumor angiogenesis and growth by nanoparticle-mediated p53 gene therapy in mice

“…Tumor cells with mutant p53 have a pro-angiogenic phenotype, marked by downregulation of angiogenic inhibitors and upregulation of pro-angiogenic factors. 9 Intratumoral delivery of p53 can potentially affect tumor neovascularization, 10, 11 in addition to directly inducing cell senescence and apoptosis of cancer cells. An understanding of the extent of the direct and “bystander” effects of p53 gene therapy is important in the development of this therapeutic approach.…”

p53 Inhibits Angiogenesis by Inducing the Production of Arresten

“…The ability of p53 to limit angiogenesis has been shown in several studies in which p53 mutation in prostate (2,3), colon (3)(4)(5), head and neck (6), and breast cancers (7) was shown to correlate with increased microvessel density (MVD). This notion was further supported by animal models showing that reversal of the angiogenic switch required p53 (8) and that p53 could induce tumor dormancy by limiting angiogenesis (9,10).…”