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DOI: 10.1055/s-2002-33189
Expression von Genen mit möglicher prognostischer Bedeutung für das Ansprechen auf Chemotherapie
bei Patienten mit Osteosarkom
Gene mit möglicher prognostischer Bedeutung beim OsteosarkomExpression of genes of potential importance in the responseto chemotherapy in osteosarcoma patients
Publikationsverlauf
Publikationsdatum:
07. August 2002 (online)
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Zusammenfassung
Hintergrund: Die Prognose von Patienten mit Osteosarkom hat sich in den letzten 30 Jahren deutlich verbessert. Dies ist in erster Linie auf den Einsatz von Chemotherapie zurückzuführen. Dennoch sprechen knapp die Hälfte der Osteosarkome schlecht auf Chemotherapie an. Marker, die das Ansprechen auf die Chemotherapie bei Diagnosestellung vorhersagen können, wären hilfreich. Patienten und Methoden: Um verschiedene Chemotherapie-assoziierte Gene auf ihre mögliche prognostische Bedeutung für das Ansprechen auf Chemotherapie zu untersuchen, wurde bei Osteosarkomen von 45 Patienten die mRNA-Expression von 8 Genen mittels semiquantitativer real-time RT-PCR gemessen und die Höhe der Expression der einzelnen Gene mit dem histologischen Ansprechen auf Chemotherapie korreliert. Ergebnisse: Bei ERCC4, einem Gen aus der Familie der Nukleotid-Exzisionsreparaturgene, fand sich eine Korrelation zwischen der Höhe der Expression und dem Ansprechen auf Chemotherapie (p = 0,0024). Bei den anderen untersuchten Genen HER-2/neu, HSP 70, GST, DHFR, BCRP, ERCC1 und Mlh1 ließ sich kein signifikanter Unterschied zwischen Respondern und Nonrespondern zeigen. Schlussfolgerung: In unserer retrospektiven Studie ließ sich eine Korrelation zwischen der Expression von ERCC4 bei Diagnosestellung und dem Grad der histologischen Nekrose nach Chemotherapie zeigen. Die prädiktive Wertigkeit von ERCC4 in Hinblick auf das Ansprechen auf Chemotherapie ist prospektiv zu überprüfen.
Abstract
Background: The prognosis of patients with osteosarcoma has considerably improved over the last 30 years, mainly due to developments in chemotherapy. However, almost half of the osteosarcomas do not respond to chemotherapy. Predictive markers for chemosensitivity at diagnosis are desirable. Patients and Methods: In order to investigate the potential of some chemotherapy-associated genes with respect to their predictive value for chemosensitivity, the mRNA expression of 8 genes was evaluated in the osteosarcomas of 45 patients and correlated to the histological response to neoadiuvant chemotherapy. Results: ERCC4, a member of the nucleotide excision repair system, showed a orrelation between expression and the histologically evaluated response to chemotherapy. The expression of the other investigated genes HER-2/neu, HSP 70, GST, DHFR, BCRP, ERCC1 and Mlh1 showed no significant correlation to response to chemotherapy. Conclusion: In our retrospective analyses, low expression of ERCC4 was shown to be related to poor response to chemotherapy. The potential value of ERCC4 as response predictor has to be investigated in a prospective study.
Schlüsselwörter
Osteosarkom - Chemotherapie-assoziierte Gene - Semiquantitative real-time RT-PCR - DNA-Reparatur
Key words
Osteosarcoma - Chemotherapy-associated genes - Real-time RT-PCR
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Dr. med. Michaela Nathrath
Kinderklinik der Technischen Universität München-Schwabing
Kölner Platz 1
80804 München
Telefon: + 49-89-30682078
Fax: + 49-89-30683947
eMail: nathrath@gsf.de