title: The expression of thrombospondin-1 and p53 in clear cell renal cell carcinoma: its relationship to angiogenesis, cell proliferation and cancer specific survival.
abstract: OBJECTIVE
  We evaluated possible associations among thrombospondin-1, p53 expression, microvessel density, cell proliferation index, nuclear grade, tumor stage and continuously coded tumor size in clear cell renal cell carcinoma. The value of thrombospondin-1 as a prognostic marker in clear cell renal cell carcinoma was examined.
  
  
  METHODS
  A total of 172 consecutive patients with clear cell renal cell carcinoma treated with radical nephrectomy were initially enrolled in the study. However, due to technical problems and lack of material 12 cases were excluded from analysis. A total of 68 patients (43%) died of renal cell carcinoma and 46 (29%) died of other diseases. Median followup for the surviving 42 patients (29%) was 13.8 years. The expression of thrombospondin-1, Ki-67 (proliferation index), p53 and microvessel density were analyzed without knowledge of the clinical outcome on formalin fixed, paraffin embedded tissues.
  
  
  RESULTS
  Low expression of thrombospondin-1 was significantly associated with advanced stage (p <0.001), high nuclear grade (p = 0.001), positive p53 status (p <0.001), high proliferation index (p = 0.001), high microvessel density (p = 0.036) and tumor progression (p = 0.006). On univariate analysis thrombospondin-1, microvessel density, proliferation index, p53 over expression, TNM stage, Fuhrman nuclear grade (p <0.001) and continuously coded tumor size (p = 0.002) had a significant impact on survival. Multivariate analysis revealed TNM stage, thrombospondin-1, p53, Ki-67 (proliferation index) and microvessel density were independent predictors of cancer specific survival.
  
  
  CONCLUSIONS
  Thrombospondin-1 expression is strongly associated with prognostic tumor features in clear cell renal cell carcinoma and is an independent prognostic factor for cancer specific survival. Our findings revealed a significant correlation among p53, proliferation index, microvessel density and thrombospondin-1 expression, and indicate that thrombospondin-1 may have an impact on angiogenesis, proliferation and tumor aggressiveness in clear cell renal cell carcinoma.
authors.affiliation: Department of Surgical Sciences, University of Bergen, Bergen, Norway.
authors.forename: Dragomir P
authors.initials: DP
authors.lastname: Zubac
authors.forename: Leif
authors.initials: L
authors.lastname: Bostad
authors.forename: Björn
authors.initials: B
authors.lastname: Kihl
authors.forename: Tomas
authors.initials: T
authors.lastname: Seidal
authors.forename: Tore
authors.initials: T
authors.lastname: Wentzel-Larsen
authors.forename: Svein A
authors.initials: SA
authors.lastname: Haukaas
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D015996:Survival Rate; D019700:Thrombospondin 1 / Q000032:analysis / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D015415:Biomarkers; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53