Che Mingxin, DeSilvio Michelle, Pollack Alan, Grignon David J, Venkatesan Varagur Mohan, Hanks Gerald E, Sandler Howard M
Department of Pathology, Wayne State University, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1117-23. doi: 10.1016/j.ijrobp.2007.04.070. Epub 2007 Aug 8.
The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca).
Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes.
Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 - 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13-2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32-4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40-10.37; p = 0.0087).
Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.
本研究的目的是验证p53作为放射治疗肿瘤学组9202中预后因素的意义,该研究比较了局部晚期前列腺癌(Pca)男性患者短期雄激素剥夺(STAD)联合放射治疗(RT)与长期雄激素剥夺+RT的疗效。
777例患者的肿瘤组织足以进行p53分析。通过免疫组织化学确定p53状态。异常p53表达定义为20%或更多细胞核阳性的肿瘤细胞。采用单因素和多因素Cox比例风险模型评估p53状态与患者预后的关系。
777例患者中有168例(21.6%)检测到异常p53,且与特定病因死亡率(调整后风险比[HR]=1.89;95%置信区间[CI]1.14 - 3.14;p = 0.014)和远处转移(调整后HR = 1.72;95%CI 1.13 - 2.62;p = 0.013)显著相关。当根据指定治疗将患者分为亚组时,只有接受STAD+RT的患者亚组中,p53状态与特定病因死亡率之间存在显著相关性(调整后HR = 2.43;95%CI = 1.32 - 4.49;p = 0.0044)。当根据p53状态将患者分为亚组时,只有p53异常的患者亚组中,指定治疗与特定病因死亡率之间存在显著相关性(调整后HR = 3.81;95%CI 1.40 - 10.37;p = 0.0087)。
异常p53是接受短期雄激素剥夺和放射治疗的前列腺癌患者的重要预后因素。长期雄激素剥夺可能显著改善p53异常患者的特定病因生存率。