Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

We investigated a dedifferentiated chondrosarcoma of a 61-year-old woman wi th an osteosarcomatous high-grade component for p53 alteration. The low-gra de cartilaginous and the high-grade osteosarcomatous components of the tumo r were macrodissected and evaluated separately by immunohistochemistry and molecular biology. We used PCR-SSCP analysis and direct sequencing to scree n exons 4-8 for p53 mutations. The p53 intron 1-polymorphism was investigat ed for loss of heterozygosity. A functionally relevant p53 missense mutatio n in codon 193 of exon 6 (A-to-T transversion) with loss of wild-type allel e was detected only in the dedifferentiated component. Using the monoclonal antibody DO-1, immunohistochemistry failed to show p53 overexpression. Thi s evidence of p53 mutation may be regarded as at least a co-factor that "sw itched" the preexisting low-grade conventional chondrosarcoma to a highly m alignant dedifferentiated tumor.