The prognostic significance of the BRAFV600E mutation in papillary thyroid carcinoma detected by mutation-specific immunohistochemistry

Aims:BRAF(V600E) mutation has been shown in a large meta-analysis to be an independent prognostic marker for papillary thyroid carcinoma (PTC) with poorer survival and higher recurrence rates.Methods:We studied prevalence of BRAF(V600E) mutation in 77 patients with PTC from an Australian cohort using competitive polymerase chain reaction (C-PCR) and immunohistochemistry (IHC) with BRAF(V600E)-specific antibody, VE1. Clinicopathological parameters, recurrence and mortality were analysed according to BRAF(V600E) mutation status.Results:Median follow-up was 84.5 months. BRAF(V600E) mutation was demonstrated in 65% of cases combining both C-PCR and IHC; in 71% (37/77) of tumours >1cm and 52% (13/25) of microcarcinomas (<1cm). IHC was positive in 69% (49/71) and C-PCR in 53% (41/77); 87% (67/77) of our patients were treated with total thyroidectomy and 65% (50/77) also had radioactive ablation. BRAF(V600E) positive tumours had a significantly higher rate of subsequent lymph node metastases (p=0.035). Significant association was found between BRAF(V600E) mutation and male sex (p=0.034), but not between age >45 years at diagnosis, size of primary tumour, extrathyroidal extension, lymph node or distant metastases or clinical stage at diagnosis.Conclusions:BRAF(V600E) mutation in PTC determined by IHC is associated with significantly increased risk of lymph node recurrence.