title: Prostate-specific membrane antigen protein expression in tumor tissue and risk of lethal prostate cancer.
abstract: BACKGROUND
  Overexpression of prostate-specific membrane antigen (PSMA) in tumor tissue and serum has been linked to increased risk of biochemical recurrence in surgically treated prostate cancer patients, but none of the studies have assessed its association with disease-specific mortality.
  
  
  METHODS
  We examined whether high PSMA protein expression in prostate tumor tissue was associated with lethal disease, and with tumor biomarkers of progression, among participants of two U.S.-based cohorts (n = 902, diagnosed 1983-2004). We used Cox proportional hazards regression to calculate multivariable HRs and 95% confidence intervals (CI) of lethal prostate cancer, defined as disease-specific death or development of distant metastases (n = 95). Partial Spearman rank correlation coefficients were used to correlate PSMA with tumor biomarkers.
  
  
  RESULTS
  During an average 13 years of follow-up, higher PSMA expression at prostatectomy was significantly associated with lethal prostate cancer (age-adjusted HRQuartile(Q)4vs.Q1 = 2.42; Ptrend < 0.01). This association was attenuated and nonsignificant (multivariable-adjusted HRQ4vs.Q1 = 1.01; Ptrend = 0.52) after further adjusting for Gleason score and prostate-specific antigen (PSA) at diagnosis. High PSMA expression was significantly (P < 0.05) correlated with higher Gleason score and PSA at diagnosis, increased tumor angiogenesis, lower vitamin D receptor and androgen receptor expression, and absence of ets-related gene (ERG) expression.
  
  
  CONCLUSIONS
  High tumor PSMA expression was not an independent predictor of lethal prostate cancer in the current study. PSMA expression likely captures, in part, malignant features of Gleason grade and tumor angiogenesis.
  
  
  CONCLUSIONS
  PSMA is not a strong candidate biomarker for predicting prostate cancer-specific mortality in surgically treated patients.
authors.affiliation: Authors' Affiliations: Departments of Epidemiology and Nutrition, Harvard School of Public Health; Channing Division of Network Medicine and Division of Preventive Medicine, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School; Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Histopathology, St. James's Hospital, Dublin, Ireland; Pathology Unit, Addarii Institute of Oncology, Sant' Orsola-Malpighi Hospital, Bologna, Italy; and Division of Medical Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Kasperzyk
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Finn
authors.forename: Richard
authors.initials: R
authors.lastname: Flavin
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.forename: Rosina
authors.initials: R
authors.lastname: Lis
authors.forename: Whitney K
authors.initials: WK
authors.lastname: Hendrickson
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
mesh_terms: D000368:Aged; D048708:Cell Growth Processes / Q000502:physiology; D015331:Cohort Studies; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000096:biosynthesis* / Q000097:blood; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D014481:United States / Q000453:epidemiology
chemical_list: D017430:Prostate-Specific Antigen