MUTATIONS OF THE P53 GENE AND P53 PROTEIN OVEREXPRESSION ARE ASSOCIATED WITH SARCOMATOID TRANSFORMATION IN RENAL-CELL CARCINOMAS

Renal cell carcinomas sometimes show sarcomatoid transformation, thus comprising both sarcomatous and carcinomatous components. Such sarcomatoid renal cell carcinomas are highly malignant with pronounced proliferative activity. The present investigation was conducted to assess the mutational status of the p53 and H-ras genes independently in carcinomatous and sarcomatous portions of individual tumors, applying PCR, subcloning, and sequencing to 14 cases. Sarcomatoid portions showed an extremely high mutation rate for the 53 gene (11 of 14, 78.6%) with two mutational hot spots at codons 278 (8 of 14, 57.1%) and 244 (6 of 11, 42.9%). Five cases showed double mutations, four cases had mutations at codons 278 and 244, and one case had mutations at codons 278 and 248. In contrast, the carcinomatous portions demonstrated a ion mutation rate for the p53 gene (2 of 14, 14.3%) and no double mutations were detected. Ten cases showed genetic heterogeneity in the p53 gene between the two tumor components. Furthermore, p53 overexpression was immunohistochemically observed only in those components with p53 mutations, mainly in the sarcomatoid portions. No B-ras mutations were observed. The findings strongly suggest that p53 mutations leading to overexpression of p53 protein are closely associated with sarcomatoid transformation in renal cell carcinomas.