Prognostic value of uPA, PAI-1, and DNA content in adult renal cell carcinoma.
OBJECTIVE
To examine whether urokinase-type plasminogen activator (uPA) and type 1 plasminogen inhibitor (PAI-1), DNA ploidy, and S-phase fraction (SPF) add supplementary prognostic information relative to stage and Fuhrman's grade in renal cell carcinoma.


METHODS
A total of 100 patients with primary renal adenocarcinoma treated by nephrectomy were followed up for a median of 42 months. Of the 100 patients, 78 with Stage M0N0-Nx tumors were studied by multivariate analysis. The study population was dichotomized on the basis of the median cytosolic uPA and PAI-1 concentrations (30 pg/mg protein and 12.7 ng/mg protein, respectively). DNA content was measured by flow cytometry (FCM) on multiple tumor samples from each patient. DNA aneuploidy was observed in 67% of cases. The SPF was calculated for aneuploid samples.


RESULTS
An FCM classification based on a combination of DNA content and SPF was obtained. High-risk patients were those with aneuploid tumors and high SPF values (greater than 1.7%) and included 23% of patients with M0N0-Nx tumors. Cytosolic uPA and PAI-1 levels were not predictive of metastasis. The stage, grade, SPF, and FCM classification were statistically significant prognostic factors in the univariate analysis, in both the overall population and the M0N0-Nx subgroup. In multivariate analysis, tumor grade and the FCM classification were the only independent predictors of disease-free survival (P = 0.018 and P = 0.046, respectively).


CONCLUSIONS
We defined a group of M0N0-Nx patients with aneuploid tumors and high SPF values who are at a high risk of metastasis and who may benefit from closer long-term follow-up.
Chautard
Denis
D
Service d'Urologie, Centre Hospitalier Universitaire, Angers, France.
Dalifard
Isabelle
I
Chassevent
Agnes
A
Guyetant
Serge
S
Daver
Alain
A
Vielle
Bruno
B
Soret
Jean Yves
JY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator