title: The superior prognostic value of humoral factors compared with molecular proliferation markers in renal cell carcinoma.
abstract: BACKGROUND
  The American Joint Committee on Cancer and the Union Internationale Contre le Cancer have acknowledged routine laboratory parameters, such as serum calcium, alkaline phosphatase, hemoglobin, and the erythrocyte sedimentation rate (ESR), as predictors of survival in patients with renal cell carcinoma. The predictive value of these parameters compared with proliferation markers, such as Ki-67, proliferating cell nuclear antigen (PCNA), topoisomerase II-alpha, and p100, has not been determined.
  
  
  METHODS
  Forty-eight consecutive patients who underwent nephrectomy for nonmetastatic renal cell carcinoma between 1990 and 1994 were observed up to 120 months postoperatively. Ten of 48 patients developed tumor progression 6-69 months after surgery. Routine preoperative laboratory parameters as well as tumor-specific data were assessed. Findings were compared with tumor proliferation indices, which were obtained by immunohistochemical staining for nuclear antigens Ki-67, PCNA, topoisomerase II-alpha, and p100 in paraffin embedded tumor tissue.
  
  
  RESULTS
  Univariate and multivariate statistical analyses demonstrated superiority of routine laboratory values compared with tumor proliferation indices in predicting progression-free survival and disease-specific death. The best predictor after tumor size and symptomatic presentation was ESR (P < 0.0001), with ESR values > 70 mm at 2 hours indicating a significantly poorer prognosis. Only the proliferation marker Ki-67 reached univariate significance at a threshold of 7%.
  
  
  CONCLUSIONS
  Routine laboratory parameters, such as alkaline phosphatase, lactate dehydrogenase, thrombocyte count, and especially ESR, provided superior long-term prognostic information for patients with nonmetastatic renal cell carcinoma compared with the molecular tumor proliferation markers Ki-67, PCNA, topoisomerase II-alpha, and p100.
authors.affiliation: Department of Urology, Saarland University, Homburg/Saar, Germany. jan.lehmann@uniklinik-saarland.de
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.forename: Nils
authors.initials: N
authors.lastname: Nürnberg
authors.forename: Uta
authors.initials: U
authors.lastname: Schnöckel
authors.forename: Uta
authors.initials: U
authors.lastname: Raffenberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Krams
authors.forename: Udo
authors.initials: U
authors.lastname: Kellner
authors.forename: Stefan
authors.initials: S
authors.lastname: Siemer
authors.forename: Klaus
authors.initials: K
authors.lastname: Weichert-Jacobsen
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000401:mortality*; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D007680:Kidney Neoplasms / Q000737:chemistry / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D004720:Endonucleases; C095221:SND1 protein, human; D004250:DNA Topoisomerases, Type II