title: Ki-67 staining index predicts distant metastasis and survival in locally advanced prostate cancer treated with radiotherapy: an analysis of patients in radiation therapy oncology group protocol 86-10.
abstract: OBJECTIVE
  Proliferative activity defined by Ki-67 staining index (SI) has been correlated with progression and prognosis in a number of malignant tumors including prostate cancer. However, few studies have examined Ki-67 SI in pretreatment diagnostic material from patients treated with definitive radiotherapy. In a prior study, we found that a Ki-67 SI of >3.5% was associated with poorer patient outcome. The goals of this analysis were to validate the prognostic value of Ki-67 SI and this cut point.
  
  
  METHODS
  Of 456 assessable patients in Radiation Therapy Oncology Group Protocol 86-10, diagnostic material from 108 patients was available for Ki-67 analysis using MIB-1 antibody. Sixty patients were treated with external beam radiotherapy (EBRT) alone, and 48 patients were treated with short-term androgen deprivation + EBRT. Median follow-up was 9 years for those living. The relationship of Ki-67 with distant metastasis (DM), disease-specific survival (DSS), and overall survival (OS) was examined.
  
  
  RESULTS
  The median Ki-67 SI was 7.1% (range, 0.2-45.5%). The 7.1% cut point was associated with DM and DSS; however, the 3.5% cut point was as strong a determinant and was the focus of this analysis. In Cox proportional hazards regression, Ki-67 SI was independently associated with DM and DSS. When the Ki-67 SI was </=3.5% and >3.5%, the 5-year risk of DM was 13.5% and 50.8% (P = 0.0005), respectively, and the 5-year risk of DSS was 97.3% and 67.7% (P = 0.0039), respectively. No association of Ki-67 SI with OS was observed.
  
  
  CONCLUSIONS
  Higher Ki-67 SI was significantly associated with a greater risk of DM and DSS in locally advanced prostate cancer after definitive EBRT or AD + EBRT.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Rile
authors.initials: R
authors.lastname: Li
authors.forename: Kateri
authors.initials: K
authors.lastname: Heydon
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Hammond
authors.forename: David J
authors.initials: DJ
authors.lastname: Grignon
authors.forename: Mack
authors.initials: M
authors.lastname: Roach
authors.forename: Harvey B
authors.initials: HB
authors.lastname: Wolkov
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
mesh_terms: D000368:Aged; D049109:Cell Proliferation; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53