title: Comparison of digital image analysis and visual scoring of KI-67 in prostate cancer prognosis after prostatectomy.
abstract: BACKGROUND
  The tumor proliferative index marker Ki-67 was shown to be associated with clinically significant outcomes in prostate cancer, but its clinical application has limitations due to lack of uniformity and consistency in quantification. Our objective was to compare the measurements obtained with digital image analysis (DIA) versus virtual microscopy (visual scoring (VS)).
  
  
  METHODS
  To do so, we compared the measurement distributions of each technique and their ability to predict clinically useful endpoints. A tissue microarray series from a cohort of 225 men who underwent radical prostatectomy was immunostained for Ki-67. The percentage of Ki-67 positive nuclei in malignant cells was assessed both by VS and DIA, and a H-score was calculated. The distribution and predictive ability of these scoring methods to predict biochemical recurrence (BCR) and death from prostate cancer (DPCa) were compared using Mann-Whitney test and C-index.
  
  
  RESULTS
  The measurements obtained with VS were similar to the DIA measurements (p = 0.73) but dissimilar to the H-score (p < 0.001). Cox regression models showed that Ki-67 was associated with BCR (HR 1.46, 95 % CI 1.10-1.94) and DPCa (HR 1.26, 95 % CI 1.06-1.50). C-indexes revealed that Ki-67 was a better predictor of DPCa (0.803, 0.8059 and 0.789; VS, DIA and H-score, respectively) than of BCR (0.625, 0.632 and 0.604; VS, DIA and H-score, respectively).
  
  
  CONCLUSIONS
  The measurement distributions and the predictive abilities of VS and DIA were similar and presented the same predictive behaviour in our cohort, supporting the role of Ki-67 proliferative index as an important prognostic factor of BCR and DPCa in prostate cancer post RP.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6656878501536663.
authors.affiliation: Cancer Research Centre, CHU de Québec, Québec, Canada. patrice.desmeules.1@ulaval.ca.|Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada. patrice.desmeules.1@ulaval.ca.
authors.forename: Patrice
authors.initials: P
authors.lastname: Desmeules
authors.affiliation: Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada. Helene.Hovington@crchudequebec.ulaval.ca.|Cancer Research Centre, CHU de Québec, Québec, Canada. Helene.Hovington@crchudequebec.ulaval.ca.
authors.forename: Hélène
authors.initials: H
authors.lastname: Hovington
authors.affiliation: Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada. moliere.nguile@gmail.com.|Cancer Research Centre, CHU de Québec, Québec, Canada. moliere.nguile@gmail.com.
authors.forename: Molière
authors.initials: M
authors.lastname: Nguilé-Makao
authors.affiliation: Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada. caroline.leger@crchudequebec.ulaval.ca.|Cancer Research Centre, CHU de Québec, Québec, Canada. caroline.leger@crchudequebec.ulaval.ca.
authors.forename: Caroline
authors.initials: C
authors.lastname: Léger
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, Canada. Andre.Caron@crchudequebec.ulaval.ca.|Population Health Unit (URESP), Centre de recherche FRQS du Centre hospitalier affilié universitaire de Québec, Québec, Canada. Andre.Caron@crchudequebec.ulaval.ca.
authors.forename: André
authors.initials: A
authors.lastname: Caron
authors.affiliation: Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada. Louis.Lacombe@crchudequebec.ulaval.ca.|Cancer Research Centre, CHU de Québec, Québec, Canada. Louis.Lacombe@crchudequebec.ulaval.ca.
authors.forename: Louis
authors.initials: L
authors.lastname: Lacombe
authors.affiliation: Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada. yves.fradet@crchudequebec.ulaval.ca.|Cancer Research Centre, CHU de Québec, Québec, Canada. yves.fradet@crchudequebec.ulaval.ca.
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.affiliation: Cancer Research Centre, CHU de Québec, Québec, Canada. Bernard.Tetu@fmed.ulaval.ca.|Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada. Bernard.Tetu@fmed.ulaval.ca.
authors.forename: Bernard
authors.initials: B
authors.lastname: Têtu
authors.affiliation: Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada. vincent.fradet@fmed.ulaval.ca.|Cancer Research Centre, CHU de Québec, Québec, Canada. vincent.fradet@fmed.ulaval.ca.|Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec - pavillon L'Hôtel-Dieu de Québec, 10 rue McMahon, Québec, QC, G1R3S1, Canada. vincent.fradet@fmed.ulaval.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fradet
mesh_terms: D000368:Aged; D049109:Cell Proliferation; D018572:Disease-Free Survival; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D012008:Recurrence; D015203:Reproducibility of Results; D012307:Risk Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen