title: Annexin A3 in urine: a highly specific noninvasive marker for prostate cancer early detection.
abstract: OBJECTIVE
  In prostate cancer cases the early diagnosis of tumors carrying a high risk of progression is of the utmost importance. There is an urgent clinical need to avoid unnecessary biopsies and subsequent overtreatment. We validated annexin A3 as a diagnostic marker for prostatic disease in typical clinical populations and relevant segments, such as patients with a negative digital rectal examination and low prostate specific antigen.
  
  
  METHODS
  We performed a blinded clinical study (ClinicalTrials.gov Identifier NCT00400894) from September 2005 to January 2007 in 591 patients who were continuously recruited from 4 European urological clinics. Urine was obtained directly after digital rectal examination and the annexin A3 concentration in urine was quantified by Western blot. Statistical analysis included combinations of annexin A3 with total, percent free, complexed and percent complexed prostate specific antigen.
  
  
  RESULTS
  Combined readouts of prostate specific antigen and urinary annexin A3 were superior to all others with an area under the ROC curve of 0.82 for a total prostate specific antigen range of 2 to 6 ng/ml, 0.83 for a total prostate specific antigen range of 4 to 10 ng/ml and 0.81 in all patients. The best performing prostate specific antigen derivative was percent free prostate specific antigen with an area under the ROC curve of 0.68 for a total prostate specific antigen range of 2 to 6 ng/ml, 0.72 for a total prostate specific antigen range of 4 to 10 ng/ml and 0.73 in all patients. Annexin A3 has an inverse relationship to cancer and, therefore, its specificity was much better than that of prostate specific antigen.
  
  
  CONCLUSIONS
  Annexin A3 quantification in urine provides a novel noninvasive biomarker with high specificity. Annexin A3 is complementary to prostate specific antigen or to any other cancer marker. It has a huge potential to avoid unnecessary biopsies with a particular strength in the clinically relevant large group of patients who have a negative digital rectal examination and prostate specific antigen in the lower range of values (2 to 10 ng/ml).
authors.affiliation: Department of Urology, Charité University Medicine in Berlin, Campus Benjamin Franklin, Berlin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
authors.forename: Gerhard P
authors.initials: GP
authors.lastname: Schwall
authors.forename: Slobodan
authors.initials: S
authors.lastname: Poznanović
authors.forename: Karlfried
authors.initials: K
authors.lastname: Groebe
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Hans
authors.initials: H
authors.lastname: Krause
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pelzer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Horninger
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Susan
authors.initials: S
authors.lastname: Feyerabend
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: André
authors.initials: A
authors.lastname: Schrattenholz
mesh_terms: D017318:Annexin A3 / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D055088:Early Detection of Cancer; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000652:urine*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D017318:Annexin A3; D017430:Prostate-Specific Antigen