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p53 status in radiation-induced soft-tissue sarcomas

p53-Status in strahleninduzierten Weichteilsarkomen

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Abstract

Background

Following therapeutic irradiation after a latency period of many years radiation-induced tumors, often sarcomas, can arise. Results of radiation-induced DNA damage can be 1. p53 over-expression, inducing growth arrest or apoptosis, and 2. occurrence of mutations, frequently including the p53 gene, as one molecular promotor for carcinogenesis. We were interested whether radiation-induced sarcomas are associated with alterations of the p53 status.

Material and Methods

Samples from 11 radiation-induced soft-tissue sarcomas (STS) were studied by a non-radioactive PCR-SSCP sequencing analysis and by immunohistochemistry with five antibodies for their p53 status.

Results

A tumor of one patient possessed a G→A transition in codon 280 (exon 8). Of 11 tumors, 9 showed nuclear p53 positivity, detected by monoclonal antibody DO-1. Of these 9 patients. 7 died during the observation period, whereas the 2 patients with DO-1 negative tumor samples are still alive.

Conclusions

p53 over-expression and p53 mutation occur in radiation-induced STS. p53 status is expected to have prognostic impact for radiation-induced STS.

Zusammenfassung

Hintergrund

Als Folge therapeutischer Bestrahlung können nach einer längeren Latenzzeit von mehreren Jahren strahleninduzierte Tumoren, oft Sarkome, entstehen. Als Ergebnis strahleninduzierter DNA-Schäden kann es 1. zu einer Überexprimierung von p53 und damit verbunden zu einer Wachstumsarretierung bzw. Apoptose kommen und 2. zum Auftreten von Mutationen führen, die häufig das p53-Gen betreffen und Promotor für eine Kanzerogenese sind. Uns interessierte, ob für strahleninduzierte Sarkome ein veränderter p53-Status vorliegt.

Patientengut und Methode

Wir untersuchten Tumorproben von elf strahleninduzierten Weichteilsarkomen in einer nichtradioaktiven PCR-SSCP-Sequenzierungsanalyse und immunhistochemisch mit Hilfe von fünf p53-Antikörpern auf Veränderungen im p53-Status.

Ergebnisse

Der Tumor eines Patienten wies eine G»A-Transition im Kodon 280 (Exon 8) auf. Neun der elf Tumoren zeigten eine p53-Kernpositivität, welche sich mit dem monoklonalen Antikörper DO-1 nachweisen ließ. Von diesen neun Patienten verstarben sieben im Beobachtungszeitraum, währenddessen die zwei Patienten mit DO-1-negativen Tumorproben noch am Leben sind.

Schlußfolgerung en

p53-Überexpression bzw.-Mutationen treten in strahleninduzierten Weichteilsarkomen auf. Es ist zu erwarten, daß der p53-Status für strahleninduzierte Weischteilsarkome von prognostischer Bedeutung ist.

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Authors and Affiliations

  1. Department of Radiotherapy, Martin Luther University of Halle-Wittenberg, Germany

    Matthias Bache & Jürgen Dunst

  2. Surgical Clinic, University of Leipzig, Germany

    Peter Würl

  3. Institute of Pathology, Magdeburger Straße 14, D-06097, Halle/Saale, Germany

    Helge Taubert, Axel Meye, Raoul Hinze, Hans-Jürgen Holzhausen, Hannelore Schmidt & Friedrich-Wilhelm Rath

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  1. Helge Taubert
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  2. Axel Meye
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  3. Matthias Bache
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  5. Hans-Jürgen Holzhausen
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  6. Hannelore Schmidt
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Correspondence to Helge Taubert.

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Taubert, H., Meye, A., Bache, M. et al. p53 status in radiation-induced soft-tissue sarcomas. Strahlenther Onkol 174, 427–430 (1998). https://doi.org/10.1007/BF03038565

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  • DOI: https://doi.org/10.1007/BF03038565

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