title: Appraisal of intratumoral microvessel density, MIB-1 score, DNA content, and p53 protein expression as prognostic indicators in patients with locally confined renal cell carcinoma.
abstract: BACKGROUND
  The prognostic values of intratumoral microvessel density (iMVD), tumor cell proliferation rate, DNA content (ploidy), and p53 protein expression are controversial or have not been well studied in patients with renal cell carcinoma (RCC) confined to the kidney.
  
  
  METHODS
  A uniform group of 52 clear cell (conventional) RCCs confined to the kidney (classified as T1N0M0 or T2N0M0) were analyzed for iMVD, MIB-1 score, DNA content, S-phase fraction, and p53 protein expression by immunohistochemical methods or flow cytometry. iMVD was evaluated in a single area (X200, 1.15 mm2) representative of the highest MVD (neovascular "hot spot") after independently highlighting endothelial cells with antibodies specific for factor VIII-related antigen (F8/86) and CD31 (JC/70A). The MIB-1 antibody (Ki-67 antigen) score was used as a marker for the tumor cell proliferation rate. DNA content and S-phase fraction were determined by flow cytometry using paraffin embedded tissue. p53 expression was assessed using the D07 antibody.
  
  
  RESULTS
  The median time of clinical follow-up was > 9 years. Eleven patients died of disease; the median time to death was 26 months. iMVD counts using antifactor VIII and anti-CD31 were tightly correlated (correlation coefficient = 0.89). S-phase fraction was higher in aneuploid tumors than in diploid tumors (mean, 12.4% vs. 4.3%; P = 0.01). Using univariate survival analyses, tumor size (stage classification pT1 vs. PT2; P = 0.01) and nuclear grade (P = 0.04) were associated with shortened survival. No statistically significant differences in survival were found for iMVD, MIB-1 score, DNA content, S-phase fraction, or p53 expression. Only two cases strongly expressed p53 protein; both tumors were of high nuclear grade. Using multivariate survival analyses, nuclear grade and tumor size were the only independent prognostic factors (best model P = 0.002).
  
  
  CONCLUSIONS
  In this study, nuclear grade and tumor size were found to be independent predictors of survival in locally confined clear cell (conventional) RCC, as has been shown previously for locally confined RCC in general. MIB-1 score, iMVD counts, DNA content, S-phase fraction, and p53 expression did not contribute additional prognostic information.
authors.affiliation: Department of Anatomic Pathology, University of California, San Francisco, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Gelb
authors.forename: D
authors.initials: D
authors.lastname: Sudilovsky
authors.forename: C D
authors.initials: CD
authors.lastname: Wu
authors.forename: L M
authors.initials: LM
authors.lastname: Weiss
authors.forename: L J
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000175:diagnosis*; D002455:Cell Division; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D007680:Kidney Neoplasms / Q000098:blood supply / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D009687:Nuclear Proteins / Q000032:analysis*; D011003:Ploidies; D011379:Prognosis; D016196:S Phase; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53