Clinical Oral Investigations

, Volume 23, Issue 1, pp 153–159 | Cite as

Immunohistochemical evaluation of Sonic Hedgehog signaling pathway proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) in sporadic and syndromic odontogenic keratocysts

  • Ana Maria Hoyos CadavidEmail author
  • E. Kaminagakura
  • M. F. S. D. Rodrigues
  • C. A. L. Pinto
  • T. H. N. Teshima
  • F. A. Alves
Original Article



The aim of this study was to compare the clinical and demographic features of 62 patients presenting sporadic odontogenic keratocysts (OKCs) or OKCs associated with nevoid basal cell carcinoma syndrome (NBCCS). In conjunction with this, we also evaluated the immunohistochemical expression of Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 and Gli3 proteins in 86 OKCs. By doing this, we add to the understanding of the biology of this type of lesion, providing tools that will help facilitate the early diagnosis of NBCCS in those patients where the first manifestation is that of OKCs.


This is a retrospective study; patients were classified into two groups: group 1 which consisted of those who were not affected by NBCCS (49 patients and 57 OKCs) and group 2 which consisted of those who were diagnosed with NBCCS (13 patients and 29 OKCs). The clinical and demographic features were studied and the immunohistochemical expression of Sonic Hedgehog proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) was analyzed in all samples.


There was an increase in the expression of three proteins in the syndromic OKC, when compared to that of sporadic cysts. Shh and Gli1 showed higher cytoplasmic expression, while Smo revealed stronger nuclear and cytoplasmic expressions.

Conclusion and clinical relevance

Our findings suggest that the expression patterns of important Shh pathway proteins can represent valuable markers for early diagnosis of NBCCS-associated OKCs, as the major criterion for the diagnosis of NBCCS is currently based on the late appearance of basal cellular carcinomas. Thus, standardizing a new diagnostic tool for diagnosis of NBCCS could be of great importance in the identification of therapeutic targets. We therefore suggest, as based on our findings, that OKCs showing high expression of Shh, Smo, and Gli1 are potentially associated with NBCCS.


Odontogenic keratocyst Nevoid basal cell carcinoma syndrome Oral diagnosis Odontogenic cysts Sonic Hedgehog 



The authors would like to thank the São Paulo State Research Foundation (FAPESP) and the Organization for the Improvement of People in Higher Education (CAPES).


This study was funded by the São Paulo Research Foundation (FAPESP))and the Organization for the Improvement of People in Higher Education (CAPES).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Stomatology, School of DentistryUniversity of Sao PauloSão PauloBrazil
  2. 2.Department of Bioscience and Oral Diagnosis, Institute of Science and TechnologyPaulista State University “Julio de Mesquita Filho” – UNESPSão José dos CamposBrazil
  3. 3.Biophotonics Applied to Health ScienceNove de Julho UniversitySão PauloBrazil
  4. 4.Department of PathologyA. C. Camargo Cancer CenterSão PauloBrazil
  5. 5.Department of StomatologyA. C. Camargo Cancer CenterSão PauloBrazil

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