title: High Ki-67 proliferative index predicts disease specific survival in patients with high-risk soft tissue sarcomas.
abstract: BACKGROUND
  Soft tissue sarcomas (STSs) are heterogeneous neoplasms that have variable clinical outcome. Several clinical parameters and few molecular markers, including Ki-67 proliferative index, have been shown to correlate with patient prognosis. To the authors' knowledge, no definitive report exists to identify one molecular marker that can be analyzed easily in a clinical setting and that predicts survival in a cohort of patients with high-risk STS of identical clinical characteristics but variable outcome.
  
  
  METHODS
  The influence of clinical prognostic factors was eliminated by selecting two patient groups with identical high-risk characteristics: large (> 10 cm), high-grade, deep, completely resected primary extremity STS (n = 47). Patients in the first group remained disease free (no evidence of disease [NED]) after primary tumor treatment (n = 19), whereas patients in the second group subsequently died of disease (DOD; n = 28). Triplicate 0.6-mm core biopsies from defined morphologic areas of paraffin embedded primary tumors were assembled on a tissue microarray and analyzed by immunohistochemistry with the MIB-1 antibody, and Ki-67 proliferative indices were correlated with patient outcome.
  
  
  RESULTS
  High Ki-67 proliferative index, defined as greater than 30% tumor cells showing nuclear immunoreactivity, was significantly more frequent in the DOD group than in the NED group and was associated with tumor-related mortality (P = 0.02). This marker identifies an especially aggressive malignant phenotype within a cohort of high-risk tumors that is based on well established clinical and pathologic parameters alone and is easy to use in a clinical setting.
  
  
  CONCLUSIONS
  On the basis of these data and previous reports, high Ki-67 proliferative index is suggested as a significant factor for predicting the prognosis of patients with high-risk STS and should be evaluated prospectively based on clinical trials.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hoos
authors.forename: A
authors.initials: A
authors.lastname: Stojadinovic
authors.forename: S
authors.initials: S
authors.lastname: Mastorides
authors.forename: M J
authors.initials: MJ
authors.lastname: Urist
authors.forename: D
authors.initials: D
authors.lastname: Polsky
authors.forename: C J
authors.initials: CJ
authors.lastname: Di Como
authors.forename: M F
authors.initials: MF
authors.lastname: Brennan
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012509:Sarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D019394:Ki-67 Antigen