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  • 1
    ISSN: 1432-2307
    Keywords: Key words Dedifferentiated chondrosarcoma ; p53 mutation ; p53 LOH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Soft-tissue tumors ; p53 gene mutation ; p53 immunohistochemistry ; PCR SSCP analysis ; DNA ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The significance ofp53 mutations in a group of 67 soft-tissue tumors was examined using single-strand conformation polymorphism and direct sequencing analysis. Molecular findings were correlated with immunohistochemical detection of thep53 protein and DNA ploidy status. Mutations of thep53 gene were detected in 13 (19.5%) out of 67 cases of soft-tissue tumors. Only there were localized outside the conservative regions of thep53 gene. Six mutations were described for the first time in these tumors. Most of the mutations were point mutations in exons 5–8 and, in one case, a deletion at the 3′-splice site of exon 5 could be demonstrated. There was no significant correlation between the occurrence ofp53 mutations and the histological grade, although a high number of mutations were defined in poorly differentiated tumors (grade 3). Molecular finding of ap53 gene mutation and immunohistochemical detection ofp53 expression did not correlate, which may be due to the high percentage of nonsense mutations in our study (50%). We confirm that only DNA sequencing allows a unique identification and differentiation of mutations in thep53 gene. Other factors may be responsible for the detection ofp53 protein in many cases. Histological grade correlated with aneuploidy. The frequency of mutations observed was in accordance with values quoted in the literature. Generally,p53 mutations andp53 overexpression are more likely to represent a late event in the oncogenesis of soft-tissue tumors.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1335
    Keywords: Key words Soft-tissue tumors ; p53 gene mutation ; p53 immunohistochemistry ; PCR SSCP analysis ; DNA ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The significance of p53 mutations in a group of 67 soft-tissue tumors was examined using single-strand conformation polymorphism and direct sequencing analysis. Molecular findings were correlated with immunohistochemical detection of the p53 protein and DNA ploidy status. Mutations of the p53 gene were detected in 13 (19.5%) out of 67 cases of soft-tissue tumors. Only three were localized outside the conservative regions of the p53 gene. Six mutations were described for the first time in these tumors. Most of the mutations were point mutations in exons 5 – 8 and, in one case, a deletion at the 3′-splice site of exon 5 could be demonstrated. There was no significant correlation between the occurrence of p53 mutations and the histological grade, although a high number of mutations were defined in poorly differentiated tumors (grade 3). Molecular finding of a p53 gene mutation and immunohistochemical detection of p53 expression did not correlate, which may be due to the high percentage of nonsense mutations in our study (50%). We confirm that only DNA sequencing allows a unique identification and differentiation of mutations in the p53 gene. Other factors may be responsible for the detection of p53 protein in many cases. Histological grade correlated with aneuploidy. The frequency of mutations observed was in accordance with values quoted in the literature. Generally, p53 mutations and p53 overexpression are more likely to represent a late event in the oncogenesis of soft-tissue tumors.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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