Kudahetti Sak, Fisher Gabrielle, Ambroisine Laurence, Foster Christopher, Reuter Victor, Eastham James, Møller Henrik, Kattan Michael W, Cooper Colin S, Scardino Peter, Cuzick Jack, Berney Daniel M
The Orchid Tissue Laboratory, Barts and The London School of Medicine and Dentistry, Centre for Molecular Oncology, London.
BJU Int. 2009 Jul;104(1):20-4. doi: 10.1111/j.1464-410X.2009.08407.x. Epub 2009 Feb 23.
OBJECTIVE To determine whether p53 is an independent biomarker of prostate cancer outcome against currently used biomarkers in a cohort of conservatively treated prostate cancers with long-term follow-up available. PATIENTS AND METHODS We examined p53 expression by immunohistochemistry in a cohort of 705 patients with clinically localized prostate cancer, who were treated conservatively. Patients were selected through UK Cancer Registries. End-points included prostate cancer death and overall death rates. Standard biological variables, including diagnostic serum PSA, contemporary Gleason scoring, clinical staging and cancer extent were available. p53 expression was measured semi-quantitatively on microscopic examination and compared with current clinical biomarkers. RESULTS p53 over expression was a significant predictor of cause-specific survival (hazard ratio [HR] 2.95, 95% CI 2.05-4.25, P < 0.001) and overall survival (HR 2.37, 95% CI 1.84-3.05, P < 0.001). In multivariate analysis including competing biological variables p53 expression was still significantly linked to prostate cancer survival (HR 1.51, 95% CI 1.04-2.19, P = 0.03) and overall survival (HR 1.57, 95% CI 1.21-2.05, P = 0.001). CONCLUSIONS We conclude that p53 may have a role in the future assessment of newly diagnosed prostate cancer, as it significantly adds to the current prognostic model.
在一组接受保守治疗且有长期随访数据的前列腺癌患者中，确定p53是否为独立于当前所用生物标志物的前列腺癌预后生物标志物。患者与方法：我们通过免疫组化检测了705例临床局限性前列腺癌保守治疗患者队列中的p53表达。患者通过英国癌症登记处选取。终点包括前列腺癌死亡率和总死亡率。可获取标准生物学变量，包括诊断时的血清前列腺特异抗原（PSA）、当代Gleason评分、临床分期和癌症范围。在显微镜检查下对p53表达进行半定量测量，并与当前临床生物标志物进行比较。结果：p53过表达是前列腺癌特异性生存（风险比[HR]2.95，95%可信区间2.05 - 4.25，P < 0.001）和总生存（HR 2.37，95%可信区间1.84 - 3.05，P < 0.001）的显著预测指标。在纳入竞争性生物学变量的多变量分析中，p53表达仍与前列腺癌生存（HR 1.51，95%可信区间1.04 - 2.19，P = 0.03）和总生存（HR 1.57，95%可信区间1.21 - 2.05，P = 0.001）显著相关。结论：我们得出结论，p53可能在新诊断前列腺癌的未来评估中发挥作用，因为它显著补充了当前的预后模型。
