title: Nuclear localization of epidermal growth factor receptor (EGFR) in ameloblastomas.
abstract: 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.
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Núbia Braga
authors.initials: NB
authors.lastname: Pereira
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Ana Carolina de Melo
authors.initials: AC
authors.lastname: do Carmo
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marina Gonçalves
authors.initials: MG
authors.lastname: Diniz
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Ricardo Santiago
authors.initials: RS
authors.lastname: Gomez
authors.affiliation: Department of Biochemistry and Immunology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Carolina Cavalieri
authors.initials: CC
authors.lastname: Gomes
mesh_terms: D000564:Ameloblastoma / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D007573:Jaw Neoplasms / Q000378:metabolism*; D034921:Lamin Type B / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009062:Mouth Neoplasms / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D034921:Lamin Type B; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: cyclin D1; epidermal growth factor receptor; nuclear EGFR; odontogenic tumors; pathology; therapy resistance