title: Ki67 and BUBR1 may discriminate clinically insignificant prostate cancer in the PSA range <4 ng/ml.
abstract: OBJECTIVE
  We aimed to evaluate the Epstein criteria and the eligibility criteria for active surveillance in the Prostate Cancer Research International study by using immunohistochemical staining.
  
  
  METHODS
  We reviewed the clinicopathological data of 119 patients who underwent prostate biopsy, with prostate-specific antigen levels being ≤4 ng/ml. The data of patients with detected prostate cancer were compared with those of patients with clinically significant prostate cancer. To discriminate insignificant prostate cancer, immunohistochemical staining for Ki67, p53, bcl-2, BUBR1, PTEN and E-cadherin was performed.
  
  
  RESULTS
  Ki67, BUBR1 and E-cadherin staining showed significant correlation with the Gleason score. Ki67 and BUBR1 staining showed significant correlations with the Epstein criteria, and Ki67, BUBR1 and E-cadherin staining correlated with the Gleason score and Prostate Cancer Research International criteria. The sensitivity and specificity of Ki67 or BUBR1 staining in discriminating the prostate cancer cases classified as clinically insignificant according to the Epstein criteria were 62.5 and 84.2%, or 57.1 and 100%, respectively. The sensitivity and specificity of Ki67, BUBR1 or E-cadherin staining in discriminating prostate cancer cases classified as clinically insignificant according to the Prostate Cancer Research International criteria were 75 and 87.5%, 66.7 and 100% or 50 and 100%, respectively. The predictive accuracy of Ki67 and BUBR1 staining was equivalently high in relation to both sets of criteria (77.6 and 83.3%, respectively).
  
  
  CONCLUSIONS
  These data could provide pathological evidence to support the suitability of the Epstein and Prostate Cancer Research International criteria. Ki67 and BUBR1 may be potential markers in selecting candidates for active surveillance.
authors.affiliation: Department of Urology, Graduate School of Medicine, Yamaguchi University, 1-1-1, Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. knag4112@yamaguchi-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagao
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Hara
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Komatsu
authors.forename: Ryo
authors.initials: R
authors.lastname: Inoue
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakano
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Baba
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D012680:Sensitivity and Specificity; D057832:Watchful Waiting
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D017430:Prostate-Specific Antigen