Mehta R, Kyshtoobayeva A, Kurosaki T, Small E J, Kim H, Stroup R, McLaren C E, Li K T, Fruehauf J P
Oncotech Incorporated, Irvine, California 92614, USA.
Clin Cancer Res. 2001 Jan;7(1):81-8.
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.
已鉴定出与前列腺癌患者预后相关的新分子因素，包括p53状态和血管生成。我们最近报道，突变型p53（mp53）与黑色素瘤和乳腺癌中血管生成内源性抑制剂血小板反应蛋白-1（TSP-1）的表达降低以及微血管密度增加有关。在本研究中，我们对原发性前列腺癌进行了类似分析，以确定这些因素是否相互关联或与患者预后相关。获取了98例原发性前列腺癌的石蜡包埋标本并进行检查，以确认组织诊断和Gleason评分。使用半定量免疫组织化学（IHC）方法测定p53、TSP-1的癌特异性水平和肿瘤血管生成情况。mp53的获得与TSP-1降低（P = 0.002）和血管生成增加（P < 0.0001）显著相关。在包括Gleason评分、临床分期和患者年龄的单变量和多变量分析中，整合mp53、TSP-1和血管生成（CD31）评分的血管生成指数被发现是生存的独立预测因子。前列腺癌血管生成指数的进一步验证可能为分层患者风险提供一种新工具。
