Research Papers: Pathology:

Nuclear localization of epidermal growth factor receptor (EGFR) in ameloblastomas

Núbia Braga Pereira, Ana Carolina de Melo do Carmo, Marina Gonçalves Diniz, Ricardo Santiago Gomez, Dawidson Assis Gomes and Carolina Cavalieri Gomes _

PDF  |  HTML  |  How to cite

Oncotarget. 2015; 6:9679-9685. https://doi.org/10.18632/oncotarget.3919

Metrics: PDF 2790 views  |   HTML 3645 views  |   ?  


Núbia Braga Pereira1, Ana Carolina de Melo do Carmo1, Marina Gonçalves Diniz2, Ricardo Santiago Gomez2, Dawidson Assis Gomes3,* and Carolina Cavalieri Gomes1,*

1 Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

2 Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

3 Department of Biochemistry and Immunology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

* These authors have contributed equally to this work

Correspondence to:

Carolina C. Gomes, email:

Keywords: odontogenic tumors, cyclin D1, epidermal growth factor receptor, nuclear EGFR, therapy resistance

Received: February 18, 2015 Accepted: April 08, 2015 Published: April 23, 2015


Background: Ameloblastoma is a locally invasive neoplasm often associated with morbidity and facial deformities, showing increased Epidermal Growth Factor Receptor (EGFR) expression. Inhibition of EGFR was suggested as a treatment option for a subset of ameloblastomas. However, there are resistance mechanisms that impair anti-EGFR therapies. One important resistance mechanism for EGFR-inhibition is the EGFR nuclear localization, which activates genes responsible for its mitogenic effects, such as Cyclin D1.

Methods: We assessed EGFR nuclear localization in encapsulated (unicystic, n = 3) and infiltrative (multicystic, n = 11) ameloblastomas and its colocalization with Cyclin D1 by using anti-EGFR and anti-lamin B1 double labeling immunofluorescence analyzed by confocal microscopy. Oral inflammatory fibrous hyperplasia and oral squamous cell carcinoma samples were used for comparison.

Results: Twelve cases of ameloblastoma exhibited nuclear EGFR colocalization with lamin B1. This positive staining was mainly observed in the ameloblast-like cells. The EGFR nuclear localization was also observed in control samples. In addition, nuclear EGFR colocalized with Cyclin D1 in ameloblastomas.

Conclusions: Nuclear EGFR occurs in ameloblastomas in association with Cyclin D1 expression, which is important in terms of tumor biology clarification and raises a concern about anti-EGFR treatment resistance in ameloblastomas.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 3919