title: Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients.
abstract: OBJECTIVE
  Neutral endopeptidase (CD10), an ectopeptidase bound to the cell surface, is thought to be a potential prognostic marker for prostate cancer.
  
  
  METHODS
  Prostate cancer patients (N = 3,261) treated by radical prostatectomy at a single institution were evaluated by using tissue microarray. Follow-up data were available for 2,385 patients. The cellular domain (membranous, membranous-cytoplasmatic, and cytoplasmatic only) of CD10 expression was analyzed immunohistochemically and correlated with various clinical and histopathologic features of the tumors.
  
  
  RESULTS
  CD10 expression was detected in 62.2% of cancer samples and occurred preferentially in higher Gleason pattern (P < 0.0001). CD10 expression positively correlated with adverse tumor features such as elevated preoperative prostate-specific antigen (PSA), higher Gleason score, and advanced stage (P < 0.0001 each). Survival analyses showed that PSA recurrence was significantly associated with the staining pattern of CD10 expression. Outcome significantly declined from negative over membranous, membranous-cytoplasmatic, to exclusively cytoplasmatic CD10 expression (P < 0.0001). In multivariate analysis, CD10 expression was an independent predictor for PSA failure (P = 0.0343).
  
  
  CONCLUSIONS
  CD10 expression is an unfavorable independent risk factor in prostate cancer. The subcellular location of CD10 protein is associated with specific clinical courses, suggesting an effect on different important biological properties of prostate cancer cells. The frequent expression of CD10 in prostate cancer and the strong association of CD10 with unfavorable tumor features may qualify this biomarker for targeted therapies.
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. achim.fleischmann@pathology.unibe.ch
authors.forename: Achim
authors.initials: A
authors.lastname: Fleischmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Jens
authors.initials: J
authors.lastname: Köllermann
authors.forename: Philipp
authors.initials: P
authors.lastname: Simon
authors.forename: Martina
authors.initials: M
authors.lastname: Mirlacher
authors.forename: Georg
authors.initials: G
authors.lastname: Salomon
authors.forename: Felix H K
authors.initials: FH
authors.lastname: Chun
authors.forename: Thomas
authors.initials: T
authors.lastname: Steuber
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000096:biosynthesis*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen; D015260:Neprilysin