MDM-2 Oncoprotein Overexpression, p53 Gene Mutation, and VEGF Up-Regulation in Angiosarcomas
Identifieur interne : 00B772 ( Main/Merge ); précédent : 00B771; suivant : 00B773MDM-2 Oncoprotein Overexpression, p53 Gene Mutation, and VEGF Up-Regulation in Angiosarcomas
Auteurs : Christian Zietz ; Matthias Rössle ; Christian Haas ; Andrea Sendelhofert ; Astrid Hirschmann ; Michael Stürzl ; Udo LöhrsSource :
- The American Journal of Pathology [ 0002-9440 ] ; 1998.
Abstract
The endothelium is one of the largest cellular compartments of the human body and has a high proliferative potential. However, angiosarcomas are among the rarest malignancies. Despite this interesting contradiction, data on growth and angiogenesis control mechanisms of angiosarcomas are scarce. In this study of 19 angiosarcomas and 10 benign vascular control lesions we investigated the sequence and expression of the
Url:
PubMed: 9811333
PubMed Central: 1876718
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Gene Mutation, and VEGF Up-Regulation in Angiosarcomas</title>
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<author><name sortKey="Rossle, Matthias" sort="Rossle, Matthias" uniqKey="Rossle M" first="Matthias" last="Rössle">Matthias Rössle</name>
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<author><name sortKey="Haas, Christian" sort="Haas, Christian" uniqKey="Haas C" first="Christian" last="Haas">Christian Haas</name>
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<author><name sortKey="Sendelhofert, Andrea" sort="Sendelhofert, Andrea" uniqKey="Sendelhofert A" first="Andrea" last="Sendelhofert">Andrea Sendelhofert</name>
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<author><name sortKey="Hirschmann, Astrid" sort="Hirschmann, Astrid" uniqKey="Hirschmann A" first="Astrid" last="Hirschmann">Astrid Hirschmann</name>
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<author><name sortKey="Sturzl, Michael" sort="Sturzl, Michael" uniqKey="Sturzl M" first="Michael" last="Stürzl">Michael Stürzl</name>
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<author><name sortKey="Lohrs, Udo" sort="Lohrs, Udo" uniqKey="Lohrs U" first="Udo" last="Löhrs">Udo Löhrs</name>
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Gene Mutation, and VEGF Up-Regulation in Angiosarcomas</title>
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<author><name sortKey="Haas, Christian" sort="Haas, Christian" uniqKey="Haas C" first="Christian" last="Haas">Christian Haas</name>
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<author><name sortKey="Sendelhofert, Andrea" sort="Sendelhofert, Andrea" uniqKey="Sendelhofert A" first="Andrea" last="Sendelhofert">Andrea Sendelhofert</name>
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<author><name sortKey="Hirschmann, Astrid" sort="Hirschmann, Astrid" uniqKey="Hirschmann A" first="Astrid" last="Hirschmann">Astrid Hirschmann</name>
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<front><div type="abstract" xml:lang="en"><p>The endothelium is one of the largest cellular compartments of the human body and has a high proliferative potential. However, angiosarcomas are among the rarest malignancies. Despite this interesting contradiction, data on growth and angiogenesis control mechanisms of angiosarcomas are scarce. In this study of 19 angiosarcomas and 10 benign vascular control lesions we investigated the sequence and expression of the <italic>p53</italic>
tumor suppressor gene and the expression of the <italic>mdm-2</italic>
proto-oncogene, which is a negative regulator of p53 activity and of the vascular endothelial growth factor (VEGF), whose expression, among other factors, is regulated by the p53/MDM-2 pathway. Ten sarcomas (53%) exibited clear nuclear p53 protein accumulation. Two of these cases revealed mutations in the sequence-specific DNA binding domain of the <italic>p53</italic>
gene. Thirteen angiosarcomas (68%) showed an increased amount of MDM-2 protein. Elevated expression of p53 and MDM-2 protein correlated with increased VEGF expression, which was found in nearly 80% of the angiosarcoma cases. Negative or clearly lower immunostaining was obtained in cases from the benign control collective. Only one case of a juvenile hemangioma reached the cutoff value of p53 positivity coincidentally with high VEGF expression. Our data suggest that the p53/MDM-2 pathway is impaired in about two-thirds (14/19) of the angiosarcomas. This may be a key event in the pathogenesis of human angiosarcomas. The increased VEGF expression observed supports this hypothesis.</p>
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