Chondrosarcoma is a primary bone tumor that has several different grad
es and variants. We evaluated 48 chondrosarcomas for p53 overexpressio
n and p53 mutations. p53 expression was evaluated with immunohistochem
istry using monoclonal antibodies PAb421, PAb1801, and PAb240. p53 mut
ations were identified with single-strand conformational polymorphism
(SSCP) and DNA sequencing in selected cases. Immunohistochemistry reve
aled nuclear staining with PAb421 and PAb 1801 in the spindle cell por
tion of one dedifferentiated chondrosarcoma. SSCP analysis was abnorma
l only in the case with positive immunostaining and localized the muta
tion to exons 7 and 8. DNA sequence analysis identified a point mutati
on of G to C in codon 276, resulting in an amino acid substitution of
proline for alanine. This point mutation has been reported previously
in other tumors but not in chondrosarcoma. Assimilation of our results
with previous studies suggests that p53 mutations are present in a mi
nority of chondrosarcomas but when present, are in higher grade chondr
osarcomas and their variants.