Independent association of angiogenesis index with outcome in prostate cancer

New molecular factors have been characterized that are associated with the prognosis of prostate carcinoma patients, including p53 status and angiogenesis. We reported recently that mutant p53 (mp53) was associated with decreased expression of an endogenous inhibitor of angiogenesis, thrombospondin-1 (TSP-1), and increased microvessel density in melanoma and breast cancer. In this study, we performed a similar analysis on primary prostate carcinoma to determine whether these factors were associated with each other or patient outcomes. Paraffin-embedded specimens of 98 cases of primary prostate carcinoma were obtained and examined to confirm tissue diagnosis and Gleason scores. Carcinoma-specific levels of p53, TSP-1, and tumor angiogenesis were determined using semiquantitative immunohistochemistry (IHC) methods. Acquisition of mp53 was significantly associated with decreased TSP-1 (P = 0.002) and increased angiogenesis (P < 0.0001). An angiogenesis index integrating mp53, TSP-1, and angiogenesis (CD31) scores was found to be an independent predictor of survival in univariate and multivariate analyses that included Gleason score, clinical stage, and patient age. Further validation of the angiogenesis index in prostate carcinoma may provide a new tool to stratify patient risk.