The Ability of Biomarkers to Predict Systemic Progression in Men with High-Risk Prostate Cancer Treated Surgically Is Dependent on ERG Status

被引:55
作者
Karnes, R. Jeffrey [2 ]
Cheville, John C. [3 ]
Ida, Cristiane M. [1 ,4 ]
Sebo, Thomas J. [3 ]
Nair, Asha A. [1 ,4 ]
Tang, Hui [5 ]
Munz, Jan-Marie [1 ,4 ]
Kosari, Farhad [1 ,4 ]
Vasmatzis, George [1 ,4 ]
机构
[1] Mayo Clin, Dept Mol Med, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Urol, Rochester, MN 55905 USA
[3] Mayo Clin, Lab Med & Pathol, Rochester, MN 55905 USA
[4] Mayo Clin, Ctr Individualized Med, Rochester, MN 55905 USA
[5] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA
关键词
TOPOISOMERASE-II-ALPHA; BREAST-CANCER; INDEPENDENTLY PREDICT; GENE AMPLIFICATION; PROTEIN EXPRESSION; PROGNOSTIC-FACTORS; FUSION; DUPLICATION; ANTIGEN; TMPRSS2;
D O I
10.1158/0008-5472.CAN-10-1358
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The objective of this study was to assess the relationship of the tumor protein levels of TOP2A and MIB-1 and ERG status with cancer-specific outcomes in men with high-risk prostate cancer treated by radical prostatectomy (RP). A 150-pair case-control study was designed from RP patients who developed systemic progression (SP) within 6 years of RP (cases) and men who were free of disease at least 8 years after RP (controls). The cases and controls were matched on conventional prognostic clinical parameters. TOP2A and MIB-1 levels were assessed by immunohistochemical methods, and ERG status was assessed by quantitative reverse transcription-PCR. The prognostic abilities of TOP2A and MIB-1 were significantly better in ERG (-) patients, and TOP2A was superior to MIB-1. In receiver operating characteristic analysis, the TOP2A and MIB-1 scores exhibited AUCs of 0.81 and 0.78 for ERG(-) patients, versus 0.67 and 0.68 for ERG(+) patients, respectively. Clinical parameters attained an AUC of 0.65 in ERG(-) patients and 0.54 in ERG(+) patients. When both markers were incorporated into a model for ERG(-) patients, the AUC increased to 0.83, with TOP2A showing a stronger association with SP than MIB-1. The time to SP was significantly associated with TOP2A; higher 5-year SP rates were observed in patients with higher TOP2A protein levels. In addition, although patient numbers are small, the response to adjuvant androgen deprivation therapy is associated with ERG status, showing more significant treatment effect in ERG(+) patients. Cancer Res; 70(22); 8994-9002. (C) 2010 AACR.
引用
收藏
页码:8994 / 9002
页数:9
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