DOC-2/DAB2 Interacting Protein Status in High-Risk Prostate Cancer Correlates With Outcome for Patients Treated With Radiation Therapy

被引:8
|
作者
Jacobs, Corbin [1 ]
Tumati, Vasu [1 ]
Kapur, Payal [2 ]
Yan, Jingsheng [3 ]
Hong, David [1 ]
Bhuiyan, Manzerul [1 ]
Xie, Xian-Jin [3 ]
Pistenmaa, David [1 ,5 ]
Yu, Lan [1 ]
Hsieh, Jer-Tsong [4 ,5 ]
Saha, Debabrata [1 ,5 ]
Kim, D. W. Nathan [1 ,5 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA
[4] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA
[5] Simmons Canc Ctr, Dallas, TX USA
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2014年 / 89卷 / 04期
关键词
DAB2IP GENE-EXPRESSION; GROUP PROTOCOL 92-02; PHASE-III TRIAL; ANDROGEN SUPPRESSION; EZH2; EXPRESSION; DOWN-REGULATION; RADIOTHERAPY; PROGRESSION; MECHANISM; ONCOLOGY;
D O I
10.1016/j.ijrobp.2014.03.035
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Methods and Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Results: Fifty-four patients with high-risk prostate cancer (stage >= T3a, or Gleason score >= 8, or prostate-specific antigen level >= 20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Conclusion: Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for determining patients with worse outcome within the high-risk prostate cancer population. (C) 2014 Elsevier Inc.
引用
收藏
页码:729 / 735
页数:7
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