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.
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.
Summarizing these results, it seems unlikely that p53 gene alterations will serve as an important new factor for the clinical prognosis of patients with renal-cell cancer.
The findings strongly suggest that p53 mutations leading to overexpression of p53 protein are closely associated with sarcomatoid transformation in renal cell carcinomas.
Our results suggest that the elevated p53 content in human renal cell carcinomas does not result from gene mutation and the p53 gene alterations are probably not an important mechanism in the development of human renal cell carcinomas.
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.
None of the 14 cases examined by SSCP analysis revealed mutations of the p53 gene, indicating that other genes at 17(p) might be important in the progression of this sub-type of RCC.
This study shows that mutation of the p53 tumour suppressor gene does not correlate with the specific loss of DNA sequences at chromosome 17 in chromophobe RCCs, nor can it be used as a prognostic parameter for RCCs in general.
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.