Tumor Biology

, Volume 37, Issue 7, pp 9587–9601 | Cite as

The sonic hedgehog signaling pathway contributes to the development of salivary gland neoplasms regardless of perineural infiltration

  • Manuela Torres Andion Vidal
  • Sílvia Vanessa Lourenço
  • Fernando Augusto Soares
  • Clarissa Araújo Gurgel
  • Eduardo J. B. Studart
  • Ludmila de Faro Valverde
  • Iguaracyra Barreto de Oliveira Araújo
  • Eduardo Antônio Gonçalves Ramos
  • Flávia Caló de Aquino Xavier
  • Jean Nunes dos Santos
Original Article


The pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are common tumors arising from salivary glands whose histopathology is heterogeneous. The sonic hedgehog signaling pathway (Hh) and signal transducer and activator of transcription 3 (STAT3) play important roles in cell proliferation, favoring tumor growth. The aim of this investigation was to study components of the Hh pathway, as well as STAT3 in salivary gland neoplasms in an attempt to add information about the biological characteristics of these neoplasms. We used 9 cases of PA, 17 cases of ACC, and 20 cases of MEC. Using immunohistochemistry, SHH, GLI1, SUFU, HHIP, and STAT3 were investigated. For comparative purposes, MCM3 (cellular proliferation marker) was also included. In PA, there was high expression of cytoplasmic SHH and SUFU and low expression of STAT3 and MCM3. In the ACC, there was high expression of GLI1, HHIP, and STAT3 and low expression of SHH, SUFU, and MCM3. In the MEC, we observed high expression of SHH, GLI1, SUFU, and HHIP and low expression of STAT3 and MCM3. There was a statistically significant difference between SHH (p = 0.0064), STAT3 (p = 0.0003), and MCM3 (p = 0.0257) when all tumors were compared and a higher expression in parenchyma for all tumors when stroma and parenchyma were compared (p < 0.05). These findings suggests a possible role of Hh pathway in the development and maintenance of the cytoarchitectural pattern of PA, ACC, and MEC, as well as the participation of STAT3 in the development of ACC, irrespective perineural infiltration.


Salivary gland tumors Hedgehog proteins STAT transcription factors Minichromosome maintenance complex component 3 


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Manuela Torres Andion Vidal
    • 1
  • Sílvia Vanessa Lourenço
    • 2
  • Fernando Augusto Soares
    • 2
  • Clarissa Araújo Gurgel
    • 1
  • Eduardo J. B. Studart
    • 3
  • Ludmila de Faro Valverde
    • 1
  • Iguaracyra Barreto de Oliveira Araújo
    • 1
    • 3
  • Eduardo Antônio Gonçalves Ramos
    • 1
  • Flávia Caló de Aquino Xavier
    • 4
  • Jean Nunes dos Santos
    • 1
    • 4
    • 5
  1. 1.Postgraduate Program in Human PathologyOswaldo Cruz FoundationSalvadorBrazil
  2. 2.A.C. Camargo Cancer CenterSão PauloBrazil
  3. 3.Department of Pathology and Forensic Medicine, School of MedicineFederal University of BahiaSalvadorBrazil
  4. 4.Laboratory of Oral Surgical Pathology, School of DentistryFederal University of BahiaSalvadorBrazil
  5. 5.Laboratório de Patologia CirúrgicaUFBASalvadorBrazil

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