INCIDENCE OF APOPTOSIS, CELL-PROLIFERATION AND P53 EXPRESSION IN RENAL-CELL CARCINOMAS

Background: Given the growing evidence that proliferation indices may be of prognostic significance in renal cell carcinoma and that paramet ers of cell loss (usually, but not exclusively due to programmed cell death) are biologically relevant, identification and quantitation of a poptosis and possible regulatory factors are of considerable clinical importance. Materials and Methods: Apoptotic cells were identified and quantified in a series of 87 curatively-resected (RO) renal cell carc inomas using the in situ end labeling method in combination with morph ological criteria. The proliferative activity was determined by immuno histochemical assessment of the MIB-1 (Ki-67) - and proliferating cell nuclear antigen (PCNA). The immunoreactivity of p53 was analysed usin g the DO7 antibody. Immunostaining of p53 has been linked to the accum ulation of mutant p53 protein. The results obtained were compared with UICC pathohistological stage and grade and finally with disease-relat ed survival rate. Results: In each carcinoma examined, we could demons trate apoptosis of varying degrees with in a range from 1 to 19 and wi th a median of 5. Immunostaining of p53 suggested the presence of muta nt p53 in 24/87 (28%). A reciprocal correlation was found between apop tosis and p53-positivity in terms of significantly less apoptosis in p 53-positive tumors. Positive statistical correlations were seen betwee n the tumor grade and MIB-1/PCNA positivity and apoptosis. In univaria te survival analysis, stage and grade, MIB-1 and PCNA index and apopto tic index were significantly related to prognosis. Multivariate Cox di sease-related survival analysis revealed that stage of disease and MIB -1 were significant independent prognostic factors Conclusions: These results indicate that apoptosis and cell proliferation are strongly re lated in renal cell carcinoma and that the presence of mutant p53 seem s to be a negative regulator of apoptosis. In univariant survival anal ysis, apoptosis was, in addition to other parameters, of prognostic si gnificance. However, multivariate analysis found that only the stage o f the disease and MIB-1 were independent prognostic factors.