Overexpression of p53 and rare genetic mutation in mesenchymal chondrosarcoma

Mesenchymal chondrosarcoma is extremely rare and accounts for less than 2% of all chondrosarcomas. The pathogenesis and the molecular genetic events w hich contribute to the development of mesenchymal chondrosarcoma are not we ll elucidated, due in part to the lack of sufficient tumor tissue available . To characterize the involvement of the p53 gene abnormality in this disea se, we analyzed expression and sequence alteration of p53 by immunohistoche mical analysis of the protein expression and quantitative DNA/PCR and PCR-S SCP assays of the gene in 33 paraffin-embedded tissue specimens. Immunohist ochemical analysis demonstrated that 19 (61.3%) of 31 had nuclear overexpre ssion of p53 while 7 (22.6%) showed cytoplasmic expression. The remaining 5 (16.1%) were negative for p53 staining. The nuclear positivity of p53 was observed within a range of 22-64% (mean 37.3%) of tumor cells and showed a positive staining in mesenchymal components as well as chondroid components . Quantitative DNA/PCR analysis revealed that 6 (18.2%) of the 33 specimens carried significantly reduced or undetectably low levels of p53 indicating the genomic deletion of the gene in these tumors. In contrast, however, DN A/PCR-SSCP analysis failed to detect any types of mutations resulting in am ino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggests that genetic alteration of p53 is a relatively rare even t in mesenchymal chondrosarcomas but substantial fraction of this type of t umors carries abnormal overexpression of p53, which might result from as ye t unidentified epigenetic mechanism(s).