title: Ki-67 and coagulative tumor necrosis are independent predictors of poor outcome for patients with clear cell renal cell carcinoma and not surrogates for each other.
abstract: BACKGROUND
  Ki-67 is a cell proliferation protein associated with aggressive clear cell renal cell carcinoma (ccRCC). A recent report suggests that Ki-67 may represent a surrogate marker for coagulative tumor necrosis. Thus, the goal was to directly test whether Ki-67 and necrosis convey similar or distinct information for the prognostic assessment of ccRCC.
  
  
  METHODS
  Tumor specimens from 741 consecutively treated patients who underwent surgery for ccRCC between 1990 and 1999 were evaluated. Tumor specimens were assessed for various clinicopathologic features, including levels of tumor cell Ki-67 expression. Associations of these features with death from RCC were evaluated using Cox proportional hazards regression models.
  
  
  RESULTS
  At last follow-up, 396 patients had died, including 238 who died from ccRCC at a median of 2.1 years after surgery. Although tumor cell Ki-67 expression and coagulative tumor necrosis were highly correlated, the prognostic information conveyed by these 2 markers failed to overlap. For the subset of patients with necrotic tumors, high levels of Ki-67 more than doubled the risk of death from RCC (risk ratio, 2.18; 95% confidence interval [CI], 1.52-3.11; P < .001). For patients with tumors lacking necrosis, high levels of Ki-67 expression were similarly correlated with an increased risk of death from RCC (risk ratio, 2.50; 95% CI, 1.66-3.77; P < .001).
  
  
  CONCLUSIONS
  Prognostic information conveyed by Ki-67 and coagulative tumor necrosis are not interchangeable. Thus, Ki-67 and coagulative tumor necrosis should not be treated as surrogates for one another and both of these features should be evaluated when generating outcome predictions for patients with ccRCC.
authors.affiliation: Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, MN 55905, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Tollefson
authors.forename: R Houston
authors.initials: RH
authors.lastname: Thompson
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sheinin
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009392:Nephrectomy / Q000379:methods / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen