title: Prognostic role of bone sialoprotein in clear cell renal carcinoma.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) follows a variable clinical course related to disease stage and metastatic spread (including to bone). Molecular and genetic factors bear prognostic significance in RCC, including proteins involved in extracellular matrix invasion. Among these, bone sialoprotein (BSP) and osteopontin (OPN) are physiologically implicated in bone metabolism, and have a prognostic role in several tumors. BSP expression was also predictive of bone spread propensity in lung and prostate carcinoma. In RCC, no data are available for BSP, while OPN has been correlated with tumor stage, grade and survival. We aimed to define the predictive (of bone spread) and prognostic role of BSP and OPN immunohistochemical expression in clear cell RCC.
  
  
  METHODS
  from a series of 305 renal tumors resected between 1993 and 2002, 75 surgically resected clear cell RCCs with tissue material, clinical data and follow-up information available, were selected for the preliminary series; a second group of 126 chemo-naïve, radically-resected, consecutive RCCs was collected as a validation series. Immunohistochemical expression of BSP and OPN on paraffinized samples was evaluated by H-score [=Σ (intensity × percentage of positively stained cells)].
  
  
  RESULTS
  In the preliminary series, BSP and OPN reactivity was found in 85% and 77% of cases, respectively. No predictive role of bone spread propensity of RCC was identified. Conversely, both BSP and OPN were significantly associated with shorter survival considering median (p=0.002) and upper quartile (p=0.03) expression values, respectively. In the validation group, a prognostic role was confirmed for BSP only (p=0.008), while OPN showed a trend of association with poorer survival (borderline p-value of 0.058).
  
  
  CONCLUSIONS
  BSP was shown for the first time to be an independent parameter associated with poor prognosis in RCC. Its coexpression with OPN identifies a subgroup of RCC having the worst outcome.
authors.affiliation: Department of Medical Sciencesand Integrated Diagnostic, University of Genoa, San Martino Hospital, Genoa, Italy. luisella.righi@unito.it
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.forename: Enrico
authors.initials: E
authors.lastname: Bollito
authors.forename: Paolo
authors.initials: P
authors.lastname: Ceppi
authors.forename: Dario
authors.initials: D
authors.lastname: Mirabelli
authors.forename: Veronica
authors.initials: V
authors.lastname: Tavaglione
authors.forename: Luigi
authors.initials: L
authors.lastname: Chiusa
authors.forename: Francesco
authors.initials: F
authors.lastname: Porpiglia
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Carlo
authors.initials: C
authors.lastname: Terrone
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism*; D011379:Prognosis
chemical_list: D058574:Integrin-Binding Sialoprotein; D053495:Osteopontin
keywords: Bone sialoprotein; osteopontin; prognosis; renal cell carcinoma