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 with an osteosarcomatous high-grade component for p53 alteration. The low-grade cartilaginous and the high-grade osteosarcomatous components of the tumor were macrodissected and evaluated separately by immunohistochemistry and molecular biology. We used PCR-SSCP analysis and direct sequencing to screen exons 4-8 for p53 mutations. The p53 intron 1-polymorphism was investigated for loss of heterozygosity. A functionally relevant p53 missense mutation in codon 193 of exon 6 (A-to-T transversion) with loss of wild-type allele was detected only in the dedifferentiated component. Using the monoclonal antibody DO-1, immunohistochemistry failed to show p53 overexpression. This evidence of p53 mutation may be regarded as at least a co-factor that "switched" the preexisting low-grade conventional chondrosarcoma to a highly malignant dedifferentiated tumor.
Grote
H J
HJ
Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
Schneider-Stock
R
R
Neumann
W
W
Roessner
A
A
D017024:Chemotherapy, Adjuvant; D002813:Chondrosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005266:Femoral Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D004273:DNA, Neoplasm