Overexpression of p53 and absent genetic mutation in clear cell chondrosarcoma

Clear cell chondrosarcoma is one of the extremely rare chondrosarcomas. The pathogenesis and the molecular genetic events, which contribute to the dev elopment of clear cell chondrosarcoma, are not well elucidated, due in part to the lack of sufficient tumor tissue available. To characterize the invo lvement of the p53 gene abnormality in this disease, we analyzed expression and sequence alteration of p53 by immunohistochemical analysis of the prot ein expression and quantitative DNA/PCR and PCR-SSCP assays of the gene in 28 paraffin-embedded tissue specimens. Immunohistochemical analysis demonst rated that 7 (25%) showed patchy positive nuclear staining for p53 and 5 (1 8%) showed diffuse positive nuclear staining patterns. Sixteen (57%) were n egative for p53 immunostaining. Quantitative DNA/PCR analysis revealed that none of the cases we studied showed significantly reduced levels of p53 am plification (<0.50), strongly suggesting an allelic deletion of the p53 gen e. In contrast, however, DNA/ PCR-SSCP analysis failed to detect any types of mutations resulting in amino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggest that genetic alteration of p5 3 is a relatively rare event in clear cell chondrosarcomas but a substantia l fraction of this type of tumors carries abnormal overexpression of p53, w hich might result from an as yet unidentified mechanism(s).