Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy

被引:65
作者
Tosoian, Jeffrey J. [1 ]
Almutairi, Fawaz [2 ]
Morais, Carlos L. [2 ]
Glavaris, Stephanie [1 ]
Hicks, Jessica [2 ]
Sundi, Debasish [1 ,3 ]
Humphreys, Elizabeth [1 ]
Han, Misop [1 ]
De Marzo, Angelo M. [2 ]
Ross, Ashley E. [1 ]
Tomlins, Scott A. [4 ,5 ]
Schaeffer, Edward M. [1 ,6 ]
Trock, Bruce J. [1 ]
Lotan, Tamara L. [2 ,7 ]
机构
[1] Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA
[2] Johns Hopkins Sch Med, Dept Pathol, 1550 Orleans St, Baltimore, MD 21231 USA
[3] UT MD Anderson Canc Ctr, Dept Urol, Houston, TX USA
[4] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA
[6] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA
[7] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA
关键词
Prostatic carcinoma; PTEN; ERG; Race; African-American; European-American; Immunohistochemistry; Radical prostatectomy; Biomarker; CANCER;
D O I
10.1016/j.eururo.2016.07.026
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
African-American (AA) men have a higher risk of lethal prostate cancer (PCa) compared to European-American (EA) men. However, the molecular basis of this difference, if any, remains unclear. In EA PCa, PTEN loss, but not ERG rearrangement, has been associated with poor outcomes in most studies. Although ERG rearrangement is less common in AA compared to EA PCa, the relative frequency of PTEN loss and the association of PTEN/ERG molecular subtypes with outcomes is unknown for AA PCa. We examined PTEN/ERG status by immunohistochemistry in self-identified AA patients undergoing radical prostatectomy at Johns Hopkins with tumor tissue available on tissue microarray (TMA; n = 169) and matched these cases by pathologic parameters to 169 EA patients from the same TMAs. The rate of PTEN loss was significantly lower in AA compared to EA PCa (18% vs 34%; p = 0.001), similar to the lower rate of ERG expression (25% vs 51%; p < 0.001). To examine the association of PTEN/ERG status with oncologic outcomes, we created an additional TMA of 87 AA tumors with Gleason score > 4 + 3 = 7. Among the total population of AA men with outcome data from all TMAs (n = 222), PTEN loss was associated with higher risk of biochemical recurrence (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33-3.82) and metastasis (HR 3.90, 95% CI 1.46-10.4) in multivariable models. Patient summary: PTEN and ERG alterations in prostate cancer are less likely in African-American than in European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes among African-American men. (C) 2016 European Association of Urology. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:697 / 700
页数:4
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