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

Jeffrey J. Tosoian, Fawaz Almutairi, Carlos L. Morais, Stephanie Glavaris, Jessica Hicks, Debasish Sundi, Elizabeth Humphreys, Misop Han, Angelo Michael Demarzo, Ashley E. Ross, Scott A. Tomlins, Edward M. Schaeffer, Bruce Trock, Tamara Lotan

Research output: Contribution to journalArticle

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 . 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. PTEN and ERG alterations in prostate cancer are less likely among African-American than European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes in African-American men.

Original languageEnglish (US)
JournalEuropean Urology
DOIs
StateAccepted/In press - 2016

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Prostatectomy
African Americans
Prostatic Neoplasms
Confidence Intervals
Immunohistochemistry
Neoplasm Metastasis
Recurrence

Keywords

  • African-American
  • Biomarker
  • ERG
  • European-American
  • Immunohistochemistry
  • Prostatic carcinoma
  • PTEN
  • Race
  • Radical prostatectomy

ASJC Scopus subject areas

  • Urology

Cite this

Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy. / Tosoian, Jeffrey J.; Almutairi, Fawaz; Morais, Carlos L.; Glavaris, Stephanie; Hicks, Jessica; Sundi, Debasish; Humphreys, Elizabeth; Han, Misop; Demarzo, Angelo Michael; Ross, Ashley E.; Tomlins, Scott A.; Schaeffer, Edward M.; Trock, Bruce; Lotan, Tamara.

In: European Urology, 2016.

Research output: Contribution to journalArticle

Tosoian, Jeffrey J. ; Almutairi, Fawaz ; Morais, Carlos L. ; Glavaris, Stephanie ; Hicks, Jessica ; Sundi, Debasish ; Humphreys, Elizabeth ; Han, Misop ; Demarzo, Angelo Michael ; Ross, Ashley E. ; Tomlins, Scott A. ; Schaeffer, Edward M. ; Trock, Bruce ; Lotan, Tamara. / Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy. In: European Urology. 2016.
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title = "Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy",
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 . 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. PTEN and ERG alterations in prostate cancer are less likely among African-American than European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes in African-American men.",
keywords = "African-American, Biomarker, ERG, European-American, Immunohistochemistry, Prostatic carcinoma, PTEN, Race, Radical prostatectomy",
author = "Tosoian, {Jeffrey J.} and Fawaz Almutairi and Morais, {Carlos L.} and Stephanie Glavaris and Jessica Hicks and Debasish Sundi and Elizabeth Humphreys and Misop Han and Demarzo, {Angelo Michael} and Ross, {Ashley E.} and Tomlins, {Scott A.} and Schaeffer, {Edward M.} and Bruce Trock and Tamara Lotan",
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T1 - Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy

AU - Tosoian, Jeffrey J.

AU - Almutairi, Fawaz

AU - Morais, Carlos L.

AU - Glavaris, Stephanie

AU - Hicks, Jessica

AU - Sundi, Debasish

AU - Humphreys, Elizabeth

AU - Han, Misop

AU - Demarzo, Angelo Michael

AU - Ross, Ashley E.

AU - Tomlins, Scott A.

AU - Schaeffer, Edward M.

AU - Trock, Bruce

AU - Lotan, Tamara

PY - 2016

Y1 - 2016

N2 - 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 . 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. PTEN and ERG alterations in prostate cancer are less likely among African-American than European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes in African-American men.

AB - 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 . 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. PTEN and ERG alterations in prostate cancer are less likely among African-American than European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes in African-American men.

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KW - Biomarker

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KW - European-American

KW - Immunohistochemistry

KW - Prostatic carcinoma

KW - PTEN

KW - Race

KW - Radical prostatectomy

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