Prognostic value of ploidy and proliferation markers in renal cell carcinoma

BACKGROUND. The prognosis for patients with renal cell carcinoma depends mainly on pathological stage and grade of the tumor at the time of surgery. Cellular proliferation may prove to be another measure for predicting biologic aggressiveness and, therefore, the prognosis. METHODS. The authors compared four different methods to assess proliferation in a series of 87 curatively resected (RO) renal cell carcinomas: flow cytometry analysis (FCM), silver-stained nucleolar organizer regions (AgNOR), and immunohistochemical assessment of the MIB-1 (Ki-67) antigen, and proliferating cell nuclear antigen (PCNA). The results obtained were compared with pathologic stage (according to the International Union Against Cancer [UICC]) and grade with disease-related survival rate; finally, we assessed whether the methods led to similar results. RESULTS. In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots in varied proportions. Statistical correlations were seen between the tumor grade, the rate of nuclear positivity for MIB-1 and PCNA, and the number of AgNOR dots. Additionally, the MIB-1 index was significantly higher in more advanced tumor stages. A good correlation between MIB-1 and AgNOR as well as for PCNA was found. In univariate survival analysis, tumor stage and grade, MIB-1 and PCNA index, and mean AgNOR number were related significantly to patient survival. On multivariate Cox disease-related survival analysis, stage of disease and MIB-1 were significant independent prognostic factors. CONCLUSIONS. These results indicated that MIB-1 immunostaining is an additional prognostic parameter for patient outcome. MIB-1 and PCNA immunostaining, as well as AgNOR, demonstrated good correlations among themselves. We failed to establish flow cytometry as a method to predict proliferative capacity or prognosis in renal cell carcinoma patients.