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Aktivierung des Sonic-hedgehog-Signalwegs in keratozystischen odontogenen Tumoren

Activation of sonic hedgehog signaling in keratocystic odontogenic tumors

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Zusammenfassung

Hintergrund

Der keratozystische odontogene Tumor (KZOT) ist ein benignes Neoplasma der Gesichtsschädelknochen, das sowohl sporadisch als auch hereditär im Rahmen des Gorlin-Goltz-Syndroms in Verbindung mit Basalzellkarzinomen der Haut auftritt. Pathogenetisch lässt sich beim Basalzellkarzinom eine aberrante Aktivierung des Sonic-hedgehog-Signalwegs (SHS) nachweisen. Da bei Patienten mit Gorlin-Goltz-Syndrom genetische Mutationen für diese Aktivierung verantwortlich sind, stellt sich die Frage, ob auch bei der Entstehung von nichtsyndromalen KZOTs eine Deregulation des SHS beteiligt ist.

Material und Methoden

In der vorliegenden Studie wurden n=131 KZOTs auf Gewebemikroarrays auf die Expression der Effektorproteine SHH, PTCH1, SMO, GLI1 und NMYC des SHS untersucht.

Ergebnisse

Die Expressionsrate der analysierten Proteine lag zwischen 67,3% (PTCH1) und 92,9% (SHH) in der epithelialen Komponente der untersuchten KZOTs. In der Stromakomponente der Tumoren fand sich signifikant seltener eine solche Expression (p jeweils <0,001).

Fazit

Die Aktivierung des SHS ist an der molekularen Pathogenese des KZOT beteiligt. Dies unterstreicht die neoplastische Natur dieser zystischen intraossären Läsion. Aufgrund der hohen Rezidivneigung bei reinen Tumorenukleationen sind resektive chirurgische Verfahren in der Therapie des KZOT vorzuziehen.

Abstract

Background

Keratocystic odontogenic tumors are benign neoplasms of the viscerocranium that occur sporadically as well as in association with Gorlin–Goltz syndrome. Multiple basal cell carcinomas of the skin are another typical feature of Gorlin–Goltz syndrome. Aberrant activation of sonic hedgehog signaling has been reported for sporadic and hereditary basal cell carcinoma caused by specific genetic mutations, but for keratocystic odontogenic tumors, the role of aberrant sonic hedgehog signaling has not yet been evaluated in detail.

Materials and methods

In the present study, 131 keratocystic odontogenic tumors were analyzed by immunohistochemistry for the expression of sonic hedgehog signaling proteins SHH, PTCH1, SMO, GLI1, and NMYC on tissue microarray sections.

Results

High expression of the analyzed proteins—between 67.3% (PTCH1) and 92.9% (SHH)—was found in the epithelial compartment of the keratocystic odontogenic tumors analyzed. In the stromal compartment of the tumors, high expression of the target proteins was found significantly less frequently (all p-values <0.001).

Conclusion

Aberrant sonic hedgehog signaling is critically involved in the molecular pathogenesis of keratocystic odontogenic tumors. This finding underlines the neoplastic character of this intraosseous lesion. Because of high recurrence rates after local excision, more radical surgical approaches are recommended for treating keratocystic odontogenic tumors.

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Authors and Affiliations

  1. Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland

    K. Freier, S. Pungs & C. Hofele

  2. Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    C. Flechtenmacher

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  1. K. Freier
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  2. S. Pungs
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  3. C. Flechtenmacher
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  4. C. Hofele
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Correspondence to K. Freier.

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Freier, K., Pungs, S., Flechtenmacher, C. et al. Aktivierung des Sonic-hedgehog-Signalwegs in keratozystischen odontogenen Tumoren. HNO 57, 345–350 (2009). https://doi.org/10.1007/s00106-008-1842-7

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  • DOI: https://doi.org/10.1007/s00106-008-1842-7

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