title: Expression of Ki-67, cyclin D1 and apoptosis markers correlated with survival in prostate cancer patients treated by radical prostatectomy.
abstract: OBJECTIVE
  The study was designed to analyse the prognostic value of proliferation markers Ki-67 and cyclin D1 and apoptosis in prostate cancer (PC) patients treated by radical prostatectomy.
  
  
  METHODS
  Two hundred and eleven patients treated by radical prostatectomy for localised prostate cancer were clinically followed up for a mean of 7.3 years. The primary histopathological specimens were re-analysed to ensure uniform histoplthological grading and pT classification. A tissue microarray construction (TMA) was used in immunohistochemisty to assess the expression of Ki-67, cyclin D1 and the apoptosis marker Tag. The results were analysed with light microscopy and the findings were compared to standard histology, pT and clinical follow-up data.
  
  
  RESULTS
  The co-expression of Ki-67 and cyclin Dl (p=0.05) was common. High fraction of Ki-67 positive cells and a high fraction of apoptotic cells were often present in same tumours (p=0.05). High apoptotic rate was related to positive surgical margin status (p=0.047). Low expression of Ki-67 was related to a low Gleason score (p<0.001), an absence of either capsule penetration (p = 0.029) or perineural invasion (p=0.004). High expression of cyclin Dl was related to perineural growth (p=0.039). Prostate specific antigen (PSA) recurrence-free survival (RFS) was predicted by Gleason grade (p<0.001) and capsule invasion (p=0.006). High expression of Ki-67 (p=0.03), as well as high apoptotic rate (p=0.04) were related to a high risk of cancer death. In multivariate analysis the seminal vesicle invasion was the only independent predictor of cancer death (p = 0.01).
  
  
  CONCLUSIONS
  The expression of Ki-67, cyclin D1 and a high apoptotic rate are related to a malignant phenotype in prostate cancer, but their prognostic value is inferior to standard histological prognostic factors.
authors.affiliation: Department of Urology, Kuopio University Hospital, Kuopio, Finland. sirpa.aaltomaa@kuh.fi
authors.forename: S
authors.initials: S
authors.lastname: Aaltomaa
authors.forename: V
authors.initials: V
authors.lastname: Kärjä
authors.forename: P
authors.initials: P
authors.lastname: Lipponen
authors.forename: T
authors.initials: T
authors.lastname: Isotalo
authors.forename: J P
authors.initials: JP
authors.lastname: Kankkunen
authors.forename: M
authors.initials: M
authors.lastname: Talja
authors.forename: R
authors.initials: R
authors.lastname: Mokka
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015331:Cohort Studies; D019938:Cyclin D1 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen; D019938:Cyclin D1