THE RELATION OF P53 PROTEIN NUCLEAR ACCUMULATION AND ANGIOGENESIS IN HUMAN PROSTATIC-CARCINOMA

All neoplasms require angiogenesis and resulting neovascularity for gr owth beyond 1 mm(2). Quantitative microvessel density (MVD) has been s hown to provide staging and prognostic significance 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 expr ession of thrombospondin-l (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 w ere investigated in men with prostate cancer. Sections from 103 radica l prostatectomy cases were evaluated with immunohistochemistry to dete ct mutant p53 proteins. Quantitative MVD was performed on the cases ex hibiting p53 positive staining and compared with negative fields of si milar Gleason grade on the same histologic sections. Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei. In 19 of these 2 0 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 mut ations of the p53 tumour suppressor gene may be associated with increa sed angiogenesis in CaP. In addition to providing staging and prognost ic information, this relationship potentially has therapeutic implicat ions.