title: Prognostic effect of neuroendocrine differentiation in prostate cancer: A critical review.
abstract: BACKGROUND
  The multiple pathways that are involved in neuroendocrine differentiation (NED) in prostate cancer (PCa) are poorly elucidated. Evidence suggests that several environmental triggers induce NED leading to the adaptation of PCa to its close environment to maintain cell proliferation. Nevertheless, there is conflicting evidence regarding the prognostic role of NED in PCa.
  
  
  METHODS
  In this review, we aimed to summarize all available data about NED and to assess the prognostic role of NED in disease progression and therapy resistance, and its role in routine clinical practice. This review was based on articles found through a PubMed literature search between 1993 and 2013. The study outcome measure was the effect of NED on oncologic outcomes at each PCa stage.
  
  
  RESULTS
  In total, 59 articles reporting on the effect of NED on oncologic outcomes have been selected. In clinical practice, immunostaining for NED markers could have interesting predictive value for assessing the oncologic outcomes in patients receiving androgen-deprivation therapy. Thus, patients with high NED burden may be candidates for more aggressive treatment strategies targeting NED pathways. Conversely, strong evidence is lacking concerning its potential independent prognostic value in hormone-naïve PCa.
  
  
  CONCLUSIONS
  Current published data are not sufficient to recommend the use of NE markers in routine practice, particularly at early PCa stage.
authors.affiliation: Centre of Urological Surgery, Dialysis and Renal Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Cristian I
authors.initials: CI
authors.lastname: Surcel
authors.affiliation: Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Inge M
authors.initials: IM
authors.lastname: van Oort
authors.affiliation: Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Sooriakumaran
authors.affiliation: Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Radiology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: De Visschere
authors.affiliation: Department of Radiology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jurgen J
authors.initials: JJ
authors.lastname: Fütterer
authors.affiliation: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Pirus
authors.initials: P
authors.lastname: Ghadjar
authors.affiliation: Department of Urology, Regio Clinic Wedel, Wedel, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Isbarn
authors.affiliation: Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
authors.affiliation: Department of Urology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Roderick C N
authors.initials: RC
authors.lastname: van den Bergh
authors.affiliation: Department of Urology, Rabin Medical Center-Beilinson, Petach-Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Yossepowitch
authors.affiliation: Department of Experimental and Clinical Medical Sciences, Urology Unit, University of Udine, Udine, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giannarini
authors.affiliation: Department of Urology, CHU Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris 7 Diderot, Paris, France. Electronic address: g.ploussard@gmail.com.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ploussard
mesh_terms: D002454:Cell Differentiation; D018450:Disease Progression; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality
keywords: Immunostaining; Neuroendocrine differentiation; Pathology; Prognosis; Prostate cancer