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Molekularbiologische und immunhistochemische Untersuchung des tp53-Gens in menschlichen Ameloblastomen

Molecular biological and immunohistochemical analysis of tp53 in human ameloblastomas

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Zusammenfassung

Fragestellung

Das Ameloblastom ist der häufigste epitheliale odontogene Tumor im Bereich des Kieferknochens. Es wächst lokal infiltrierend und neigt zu Rezidiven. Fälle einer malignen Transformation und das Auftreten von Fernmetastasen sind beschrieben. Immunhistochemische Untersuchungen zeigen eine erhöhte Expression von P53-Protein in Ameloblastomen. Mutationen des tp53-Tumorsuppressorgens wurden in einer Vielzahl menschlicher Tumoren nachgewiesen. In der vorliegenden Studie wurden histologische Gewebeschnitte auf die Expression von P53-Protein untersucht und das tp53-Gen betroffener Patienten einer Mutationsanalyse unterzogen.

Material und Methoden

Die Tumor-DNS von 29 Ameloblastompatienten wurde auf Mutationen in den Exons 5 bis 8 des tp53-Tumorsuppressorgens mittels PCR, SSCP- und Sequenzanalyse untersucht. Schnittpräparate dieser Tumoren wurden immunhistochemisch auf eine Überexpression von P53-Protein überprüft.

Ergebnisse

Erstmalig konnten zwei tp53-Mutationen (6,9%) in Ameloblastomen nachgewiesen werden. 58,6% der Tumoren zeigten eine Immunreaktivität für P53-Protein. Es bestand eine statistisch signifikante positive Korrelation (Fisher’s Exact-Test p<0,0148) zwischen einer erhöhten Zahl P53-positiver Tumorzellen und dem Auftreten eines Rezidives.

Schlussfolgerung

Im Hinblick auf das unsichere postoperative Verhalten des Ameloblastoms könnte der immunhistochemische Nachweis von mehr als 10% P53-positiver Tumorzellen prognostische Hinweise auf eine Rezidivneigung liefern.

Abstract

Aim

Ameloblastoma is the most frequent epithelial tumor of the jaws. The spread is locally invasive and it tends to recur. Malignant transformation and occurrence of metastases has been described. Immunohistochemical analysis shows an enhanced expression of P53 protein in ameloblastomas. Mutation of the tp53 tumor suppressor gene was verified in several human tumors. In this study histological sections were analyzed for the expression of P53 protein and the tp53 gene was examined for mutations.

Material and methods

Tumor DNA from 29 patients with an ameloblastoma was examined for mutations in exons 5 to 8 of the tp53 tumor suppressor gene using PCR, SSCP,- and sequential analysis. Histological sections of the tumors were analyzed immunohistochemically for an overexpression of P53 protein.

Results

Two tp53 mutations (6.9%) in ameloblastomas were verified for the first time. In all 58.6% of the tumors showed an immunoreactivity for P53 protein. There was a statistically significant positive correlation (Fisher’s exact test p<0.0148) between an increased number of P53-positive tumor cells and the appearance of recurrence.

Discussion

In the face of the uncertain postoperative behavior of ameloblastomas, the immunohistochemical verification of more than 10% P53-positive tumor cells may give a prognostic indication for a tendency to recurrence.

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Authors and Affiliations

  1. Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie, Rheinische Friedrich-Wilhelms-Universität Bonn

    T. Appel, M. Martini & S. Bergé

  2. Abteilung für Mund-, Kiefer- und Gesichtschirurgie, Bundeswehrzentralkrankenhaus Koblenz

    R. Gath

  3. Pathologisches Institut, Rheinische Friedrich-Wilhelms-Universität Bonn

    N. Wernert

  4. Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freud-Straße 25, 53105, Bonn

    T. Appel

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  1. T. Appel
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  4. M. Martini
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Correspondence to T. Appel.

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Appel, T., Gath, R., Wernert, N. et al. Molekularbiologische und immunhistochemische Untersuchung des tp53-Gens in menschlichen Ameloblastomen. Mund Kiefer GesichtsChir 8, 167–172 (2004). https://doi.org/10.1007/s10006-004-0539-7

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