The aim of this study was to investigate whether the expression of BRAF‐V600E determines an aggressive clinical and molecular presentation of ameloblastoma. Methods and results Ninety‐three cases of solid ameloblastomas were arranged in a 1.0‐mm tissue microarray (TMA) block. Immunohistochemistry...

The aim of this study was to investigate whether the expression of BRAF‐V600E determines an aggressive clinical and molecular presentation of ameloblastoma. Methods and 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

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