BRAF-V600E expression correlates with ameloblastoma aggressiveness.
OBJECTIVE
The aim of this study was to investigate whether the expression of BRAF-V600E determines an aggressive clinical and molecular presentation of ameloblastoma.


RESULTS
Ninety-three cases of solid ameloblastomas were arranged in a 1.0-mm tissue microarray (TMA) block. Immunohistochemistry against a large panel of cytokeratins (CK), epidermal growth factor receptor (EGFR), parathyroid hormone-related peptide (PTHrP), syndecan-1, Ki67, p53 and BRAF-V600E were performed. Clinicopathological parameters, including sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic pattern, vestibular/lingual and basal cortical plates disruption and follow-up data, were obtained from patients' medical records. Immunoexpression of BRAF-V600E was investigated in 73 cases that remained available in TMA sections. Our results indicated that 46.6% (34 cases) demonstrated cytoplasm positivity (six weak and 28 strong positivity). BRAF-V600E expression was associated significantly with the expression of CK8 (P = 0.00077), CK16 (P = 0.05), PTHrP (P = 0.0082) and p53 (P = 0.0087). Additionally, a significant association was seen with the presence of recurrences (P = 0.0008), multilocular radiographic appearance (P = 0.044) and disruption of basal bone cortical (P = 0.05). Univariate analysis showed that BRAF-positive cases (P = 0.001), EGFR-negative/weak positive cases (P = 0.03) and multilocular tumours (P = 0.04) had a significantly lower disease-free survival rate, but these parameters were not considered independent prognostic factors in the multivariate analysis (P > 0.05).


CONCLUSIONS
Our findings suggest an association of BRAF-V600E with parameters of a more aggressive behaviour of ameloblastoma, supporting the future use of BRAF inhibitors for targeted therapy of this neoplasm.
Department of Oral Medicine, Sírio-Libanês Hospital, São Paulo, Brazil.
Eduardo R
ER
Fregnani
Oral Pathology, Dental School, Federal University of Pernambuco, Recife, Brazil.
Danyel E da Cruz
DE
Perez
Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
Oslei
O
Paes de Almeida
Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
Felipe Paiva
FP
Fonseca
Department of Pathology, A C Camargo Cancer Center, São Paulo, Brazil.
Fernando A
FA
Soares
Clinical Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Gilberto
G
Castro-Junior
Department of Oral Medicine, A C Camargo Cancer Center, São Paulo, Brazil.
Fábio A
FA
Alves
D000328:Adult; D000564:Ameloblastoma / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000401:mortality / Q000473:pathology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf

BRAF
; ameloblastoma; mitogen-activated protein kinase; odontogenic tumours