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<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.
  
  
  
  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.
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Tosoian
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Almutairi
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Morais
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Glavaris
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hicks
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Urology, UT MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Debasish
authors.initials: D
authors.lastname: Sundi
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Humphreys
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Ross
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Urology, Northwestern University, Chicago, IL, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schaeffer
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Trock
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: tlotan1@jhmi.edu.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lotan
mesh_terms: D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data*; D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D000071230:Transcriptional Regulator ERG / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data*
chemical_list: C072312:ERG protein, human; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: African-American; Biomarker; ERG; European-American; Immunohistochemistry; PTEN; Prostatic carcinoma; Race; Radical prostatectomy