title: Ki67 staining index and neuroendocrine differentiation aggravate adverse prognostic parameters in prostate cancer and are characterized by negligible inter-observer variability.
abstract: BACKGROUND
  This study aims to clarify whether neuroendocrine differentiation (NED) and/or proliferation activity assessed by means of Ki67 staining index (Ki67SI) might aggravate other established adverse prognostic parameters commonly used for predicting outcome in surgically treated prostate cancer, and to assess inter-observer variability in assigning NED and Ki67 SI.
  
  
  METHODS
  A total of 528 patients surgically treated due to prostate cancer were evaluated in this study. Relevant data were retrospectively obtained by chart review. Immunostaining with antibodies directed against Chromogranin A and Ki67 was performed on archived surgical material, and was evaluated by two independent histopathologists blinded to the specimens. Surveying a median postsurgical follow-up of 46.4 months, postsurgical serum PSA-levels were regularly documented for identifying biochemical progress. Multivariate analysis was performed by means of the Cox regression hazards regression method to evaluate possible aggravations of established adverse prognostic parameters (nodal status, tumour stage, pretherapeutic PSA-level, and Gleason score) by NED and/or Ki67SI. Ki67 SI and NED were shown to significantly aggravate these established adverse prognostic parameters, and were found to be characterized by negligible inter-observer variability.
  
  
  CONCLUSIONS
  Ki67 SI and NED should be advocated to be rendered by the histopathologist because both parameters can be immunohistochemically determined without much additional expense in time and cost involved. This concept is rewarded by an additional gain of prognostic accuracy in evaluating individual risk profile after surgery.
authors.affiliation: Department of Pathology, HELIOS Klinikum Bad Saarow, Charité-University Medicine Teaching Hospital, Pieskower Strasse 33, 15526 Bad Saarow, Germany. sven.gunia@helios-kliniken.de
authors.forename: Sven
authors.initials: S
authors.lastname: Gunia
authors.forename: Knut
authors.initials: K
authors.lastname: Albrecht
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Ecke
authors.forename: Volker
authors.initials: V
authors.lastname: Loy
authors.forename: Jörg
authors.initials: J
authors.lastname: Linke
authors.forename: Michael
authors.initials: M
authors.lastname: Siegsmund
authors.forename: Matthias
authors.initials: M
authors.lastname: May
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055099:Neuroendocrine Cells / Q000378:metabolism / Q000473:pathology*; D015588:Observer Variation; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D017430:Prostate-Specific Antigen