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

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          Abstract

          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.

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          Author and article information

          Journal
          7512719
          3630
          Eur Urol
          Eur. Urol.
          European urology
          0302-2838
          1873-7560
          27 July 2016
          28 July 2016
          May 2017
          01 May 2018
          : 71
          : 5
          : 697-700
          Affiliations
          [a ]Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA
          [b ]Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
          [c ]Department of Urology, UT MD Anderson Cancer Center, Houston, TX, USA
          [d ]Department of Pathology, University of Michigan, Ann Arbor, MI, USA
          [e ]Department of Urology, University of Michigan, Ann Arbor, MI, USA
          [f ]Department of Urology, Northwestern University, Chicago, IL, USA
          [g ]Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA
          Author notes
          [* ]Corresponding author. Department of Urology, Johns Hopkins School of Medicine, 1550 Orleans Street, Baltimore, MD 21231, USA. Tel. +1 410 6149196; Fax: +1 410 6140671. tlotan1@ 123456jhmi.edu (T. Lotan)
          [†]

          These author contributed equally.

          Article
          PMC5274596 PMC5274596 5274596 nihpa805280
          10.1016/j.eururo.2016.07.026
          5274596
          27477529
          Categories
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