We examined 33 patients with renal cell carcinoma and 29 with bladder cancer; heterozygosity in the p53 gene was lost in 60% (6 of 10 cases) and 73% (8 of 11 cases) of the renal and bladder tumors, respectively.
The association of genetic predisposition to urologic cancers with p53 gene codon 72 polymorphism is not so clear as the previous study of Japanese lung cancer patients, but this polymorphism may play some role in urothelial cancers and renal cell carcinoma, in which smoking is an epidemiological risk factor.
We conclude that the p53 gene mutation does not play a role in the development of the majority of cases of renal cell carcinoma and that there may be another tumor suppressor gene on 17p.
Statistical analysis revealed a close relationship between p53 protein expression and the tumor grade, as well as a significant association of HER-2 protein expression and gene amplification with the tumor stage of RCC.
Tumor progression in renal cell carcinoma (RCC) can be explained by a multistep model, in which the activation of certain oncogenes such as c-neu and c-fos appear to be early events in tumorigenesis, while the expression of p53 and pan-ras are found in advanced stages.
Immunoblots of RCC samples detected a normal size WT I protein and reciprocal antibody immunoprecipitations of RCC cell extracts indicated that WT I interacts with p53 as has been demonstrated for normal human fetal kidney.
These findings suggest that, in RCC, inactivation of p53 might contribute to progression of the disease but inactivation of p21WAF1 and bax are not likely to play significant roles in the defective p53 pathway.
RCC in transplants shared several clinicopathological features with those in dialysis patients, which included small size and multiplicity of tumor, relatively high frequency of presence of ACDK, and papillary type of RCC. p53 gene mutations were infrequent in RCC of any clinical setting.
These data suggest that: (a) mutation of p53 contributes to the overexpression of IL-6 in RCC; and (b) wt p53 represses IL-6 expression, at least in part, by interfering with specific transcription factor binding to the IL-6 promoter.
Remarkably, cells of normal kidney epithelium also caused partial p53 repression in cell fusion experiments, suggesting that RCC-specific p53 repression may be based on an unknown dominant mechanism also acting in normal kidney tissue.