Head and Neck Pathology

, Volume 13, Issue 4, pp 535–542 | Cite as

Immunolocalization of Cancer Stem Cells Marker ALDH1 and its Association with Tumor Budding in Oral Squamous Cell Carcinoma

  • Helvécio Marangon Junior
  • Victória Vasconcellos Moreira Melo
  • Ângela Braga Caixeta
  • Giovanna Ribeiro Souto
  • Paulo Eduardo Alencar Souza
  • Maria Cássia Ferreira de Aguiar
  • Martinho Campolina Rebello HortaEmail author
Original Paper


Tumor budding is a prognostic marker for oral squamous cell carcinoma (OSCC) characterized by the presence of isolated or small clusters of neoplastic cells at the tumor invasive front. Aldehyde dehydrogenase-1 (ALDH1) is associated with tumorigenesis, linked to treatment resistance and shown to identify cancer stem cells (CSC)-like cells. This study aimed to evaluate the expression of ALDH1 and its association with tumor budding in OSCC. Immunohistochemistry was employed in 163 OSCC samples to identify pancytokeratin (AE1/AE3) and ALDH1. While pancytokeratin (AE1/AE3) identified squamous tumor buds, the CSC-like cells were identified using ALDH1. A Chi square test was used to evaluate association between ALDH1 expression and tumor budding, while McNemar’s test was used to identify differences in ALDH1 expression between the budding area and the area outside the budding. A positive expression of ALDH1 was observed in 47.24% of the samples and in 70% of anatomic locations affected. No association was observed between ALDH1 expression and tumor budding (p > 0.05). In tumors with high-intensity tumor budding, ALDH1 expression was higher in the budding area than in the area outside the budding (p < 0.05). The finding that tumor bud cells in OSCC show phenotypic characteristics of CSC-like cells reinforces the relevance of tumor budding in determining the biological behavior of this malignant neoplasm. Moreover, the presence of CSC-like cells in nearly half of evaluated samples of OSCC and in most of the affected anatomic locations is in accordance with the CSC model of oral carcinogenesis.


Oral cancer Squamous cell carcinoma Cancer stem cells Aldehyde dehydrogenase-1 Tumor budding 



This study was supported by Grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG CDS-APQ-01806/14 and FAPEMIG CDS-PPM-00653-16). The authors are grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). MCRH is a research fellow of FAPEMIG (CDS-PPM-00653-16); MCFA is a research fellow of CNPq; HMJ had a CAPES fellowship for this study; and VVMM and ABC had PROBIC-FAPEMIG fellowships (PROBIC 10499/2016). The authors also wish to thank the invaluable technical assistance provided by Mrs. Maria Reni Gonçalves Moitinha and Ms. Andreia Alves Cardoso.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Helvécio Marangon Junior
    • 1
    • 2
  • Victória Vasconcellos Moreira Melo
    • 1
  • Ângela Braga Caixeta
    • 1
  • Giovanna Ribeiro Souto
    • 1
  • Paulo Eduardo Alencar Souza
    • 1
  • Maria Cássia Ferreira de Aguiar
    • 3
  • Martinho Campolina Rebello Horta
    • 1
    • 4
    Email author
  1. 1.Oral Pathology Section, School of DentistryPontifical Catholic University of Minas Gerais (PUC Minas)Belo HorizonteBrazil
  2. 2.Centro Universitário de Patos de Minas (UNIPAM)Patos de MinasBrazil
  3. 3.Department of Oral Diagnosis and Pathology, School of DentistryFederal University of Minas Gerais (UFMG)Belo HorizonteBrazil
  4. 4.Departamento de OdontologiaPontifícia Universidade Católica de Minas GeraisBelo HorizonteBrazil

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