Infrequent alteration of p53 pathway in metastatic renal cell carcinoma.

Renal-cell carcinoma (RCC) is known to be highly resistant to conventional chemotherapy and irradiation suggesting that RCC cells do not easily undergo apoptosis, though p53 mutation is an infrequent event in RCC. p53 is responsible for the expression of p21WAF1 and bax genes, and these expressions are involved in the G1 arrest or apoptosis when cells are exposed to genotoxic stimuli. These gene mutations have been detected and their dysfunction may lead to accumulation of genomic alterations. We investigated the p53, p21WAF1 and bax gene mutations in 5 patients who had primary RCC and metastatic tumors. In one case only the metastatic tumor had non-sense transversion in the p53 gene, whereas the primary tumor showed no p53 gene mutation. no p21WAF1 and bax mutations were detected in any primary RCC or metastatic tumors. 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.