Severi Gianluca, FitzGerald Liesel M, Muller David C, Pedersen John, Longano Anthony, Southey Melissa C, Hopper John L, English Dallas R, Giles Graham G, Mills John
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, 3004, Australia; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
Cancer Med. 2014 Oct;3(5):1266-74. doi: 10.1002/cam4.281. Epub 2014 Jun 7.
Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, "cases" (N = 83), were matched to "referents" (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14-5.54, P = 0.02 and 3.08, 95% CI 1.41-6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20-0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage.
只有少数前列腺癌会导致死亡。由于在诊断时除了 Gleason 评分外没有其他侵袭性组织生物标志物，许多非致命性癌症都接受了积极治疗。我们评估了一组在先前研究中与一系列疾病结局相关的生物标志物是否能够预测局限性疾病男性前列腺癌死亡情况。采用病例对照设计，从三项澳大利亚流行病学研究中确定研究对象。死于前列腺癌的男性，即“病例”（N = 83），通过发病密度抽样与未死于前列腺癌的“对照”（N = 232）进行匹配。获取诊断组织，通过半定量免疫组织化学（IHC）评估 AZGP1、MUC1、NKX3.1、p53 和 PTEN 的表达。使用泊松回归估计经年龄、Gleason 评分和分期调整后的死亡率比（MRR），并估计生存概率。MUC1 和 p53 的表达与死亡率增加相关（MRR 分别为 2.51，95%CI 1.14 - 5.54，P = 0.02；以及 3.08，95%CI 1.41 - 6.95，P = 0.005），而 AZGP1 的表达与死亡率降低相关（MRR 0.44，95%CI 0.20 - 0.96，P = 0.04）。在联合模型下分析所有标志物表明，这三种标志物是前列腺癌死亡和生存的独立预测因子。对于诊断时患有局限性疾病的男性，通过 IHC 评估诊断组织中 AZGP1、MUC1 和 p53 的表达可能会改善仅基于 Gleason 评分和临床分期对前列腺癌死亡风险的估计。
