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 parameters of cell loss (usually, but not exclusively due to programmed cell death) are biologically relevant, identification and quantitation of apoptosis 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 carcinomas using the in situ end labeling method in combination with morphological criteria. The proliferative activity was determined by immunohistochemical assessment of the MIB-1 (Ki-67) - and proliferating cell nuclear antigen (PCNA). The immunoreactivity of p53 was analysed using the DO7 antibody. Immunostaining of p53 has been linked to the accumulation of mutant p53 protein. The results obtained were compared with UICC pathohistological stage and grade and finally with disease-related survival rate. Results: In each carcinoma examined, we could demonstrate apoptosis of varying degrees with in a range from 1 to 19 and with a median of 5. Immunostaining of p53 suggested the presence of mutant p53 in 24/87 (28%). A reciprocal correlation was found between apoptosis and p53-positivity in terms of significantly less apoptosis in p53-positive tumors. Positive statistical correlations were seen between the tumor grade and MIB-1/PCNA positivity and apoptosis. In univariate survival analysis, stage and grade, MIB-1 and PCNA index and apoptotic index were significantly related to prognosis. Multivariate Cox disease-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 related in renal cell carcinoma and that the presence of mutant p53 seems to be a negative regulator of apoptosis. In univariant survival analysis, apoptosis was, in addition to other parameters, of prognostic significance. However, multivariate analysis found that only the stage of the disease and MIB-1 were independent prognostic factors.