title: The prognostic value of erythrocyte polyamine in the post-nephrectomy stratification of renal cell carcinoma specific mortality.
abstract: OBJECTIVE
  The polyamines spermine and spermidine are ubiquitous polycationic structures which are essential for cell proliferation and differentiation. Circulating polyamines, spermine and spermidine, represent valuable prognostic markers in prostate cancer, acute leukemia and supratentorial malignant glioma. We tested whether spermine and spermidine could improve the prognostic ability of several established predictors of cancer specific mortality after partial or radical nephrectomy for renal cell carcinoma.
  
  
  METHODS
  Testing was performed on 399 patients with stages T(1-4), N(0-2), M(0-1) renal cell carcinoma who were treated with radical or partial nephrectomy at a single institution between 1990 and 2007. Univariable and multivariable Cox regression models tested the prognostic ability of spermine and spermidine levels in cancer specific mortality predictions. Covariates consisted of TNM stage, Fuhrman grade, tumor size and symptom classification. Harrell's concordance index (c-index) quantified accuracy and 200 bootstrap resamples were used to correct for overfit bias.
  
  
  RESULTS
  The 5-year cancer specific mortality-free survival of patients with spermine levels 3 or less, 3.1 to 8, 8.1 to 13 and greater than 13 nmol/8x10(9) erythrocytes was 88.8%, 75.8%, 40.2% and 21.8%, respectively. Similarly the 5-year cancer specific mortality-free survival of patients with spermidine levels 12 or less, 12.1 to 15, 15.1 to 21 and greater than 21 nmol/8x10(9) erythrocytes was 79.0%, 56.6%, 53.2% and 27.4%, respectively. On multivariable analyses addressing cancer specific mortality after surgery spermine (p = 0.007) and spermidine (p = 0.04) achieved independent predictor status. Consideration of spermine and spermidine also improved the accuracy of established cancer specific mortality predictors by 2.2% (p <0.001).
  
  
  CONCLUSIONS
  Spermine and spermidine may significantly improve the prognostic value of established cancer specific mortality predictors after partial or radical nephrectomy for all stages of renal cell carcinoma. Independent external validation of our findings is required.
authors.affiliation: Rennes University Hospital, Rennes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bigot
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lughezzani
authors.forename: Pierre
authors.initials: P
authors.lastname: Karakiewicz
authors.forename: Paul
authors.initials: P
authors.lastname: Perrotte
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: Veronique
authors.initials: V
authors.lastname: Catros-Quemener
authors.forename: Francoise
authors.initials: F
authors.lastname: Bouet
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Moulinoux
authors.forename: Bernard
authors.initials: B
authors.lastname: Cipolla
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Patard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000401:mortality* / Q000601:surgery; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D013095:Spermidine / Q000097:blood*; D013096:Spermine / Q000097:blood*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D013096:Spermine; D013095:Spermidine