The superior prognostic value of humoral factors compared with molecular proliferation markers in renal cell carcinoma.
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.
Lehmann
Jan
J
Department of Urology, Saarland University, Homburg/Saar, Germany. jan.lehmann@uniklinik-saarland.de
Retz
Margitta
M
Nürnberg
Nils
N
Schnöckel
Uta
U
Raffenberg
Uta
U
Krams
Matthias
M
Kellner
Udo
U
Siemer
Stefan
S
Weichert-Jacobsen
Klaus
K
Stöckle
Michael
M
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
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