MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02
MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02
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DOI：
10.1200/jco.2008.19.8267
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发表时间：
2009-07-01
影响因子：
45.3
通讯作者：
Pollack, Alan
中科院分区：
文献类型：
--
作者：
Khor, Li-Yan;Bae, Kyounghwa;Pollack, Alan
目的MDM2 调节 p53，后者控制细胞周期停滞和细胞凋亡。这两种蛋白以及 Ki-67（一种已确定的转移的强决定因素）在预测接受或不接受短期雄激素剥夺 (STAD) 的放射治疗 (RT) 治疗的男性的结果方面显示出了前景。本报告比较了这些生物标志物的异常表达在评估接受 RTOG 92-02 治疗的男性队列进展中的效用。 患者和方法 在 478 例患者病例中，有足够的组织用于免疫组织化学分析 p53、Ki-67 和 MDM2。手动或通过图像分析量化肿瘤核染色阳性（PSP）的百分比，并通过图像分析量化每个样本的平均强度评分（MIS）。 Cox 回归模型用于估计总体死亡率 (OM)，Fine 和 Gray 回归应用于远处转移 (DM) 和原因特异性死亡率 (CSM) 的终点。结果在调整所有标志物和治疗协变量的多变量分析中，MDM2 过表达与 DM (P = .02) 和 OM (P = .003) 显着相关，Ki-67 过表达与 DM 显着相关 (P < .0001)、CSM (P = .0007) 和 OM (P = .01)。 P53 过度表达与 OM 显着相关 (P = .02)。当综合考虑时，高水平的 Ki-67 和 MDM2 过度表达与所有终点的失败率显着增加相关（对于 DM、CSM 和 OM，P < .001）。 结论 MDM2 和 Ki-67 的联合表达水平与远处转移和死亡率独立相关，如果得到验证，可以考虑用于临床试验中前列腺癌患者的风险分层。
PurposeMDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02.Patients and MethodsAdequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Gray's regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM).ResultsIn multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM).ConclusionCombined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.