BRAF in primary and recurrent papillary thyroid cancers: the relationship with 131I and 2-[18F]fluoro-2-deoxy-D-glucose uptake ability

Objective: BRAF V600E is a potential marker of poor prognosis in papillary thyroid cancers (PTC). In a previous report, we showed that recurrent PTC with no radioiodine (I-131) uptake are frequently associated with BRAF mutations, a low expression of thyroid-related genes and a high expression of glucose type-1 transporter gene. Aim: The aim of the present study was to assess BRAF status in a large series of recurrent PTC patients, considering paired primary and recurrent cancers. The BRAF genotype was correlated with the ability to concentrate I-131 and/or 2-[F-18]fluoro-2-deoxi-D-glucose (F-18-FDG) in the recurrent cancers, serum markers of recurrence, and patient outcome. Design and methods: We studied 50 PTC patients with recurrent cervical disease submitted to a re-intervention, followed up in median for 9 years. BRAF analysis was conducted by direct sequencing and mutant allele-specific PCR amplification. In 18 cases, molecular analysis was also assessed in the primary cancer. Out of 50 patients, 30 underwent F-18-FDG-positron emission tomography-computed tomography. Results: BRAF V600E-positive recurrent patients were found I-131-negative in 94% of cases (P<0.001); 73% of the cancers carrying BRAF V600E were both I-131-negative and F-18-FDG positive. In paired primary and recurrent PTC, BRAF V600E was observed in 79% of the primary cancers and 84% of their recurrences. Three patients with I-131-negative and BRAF V600E-positive recurrent cancers deceased during follow-up. Conclusions: BRAF mutations are more common in thyroid recurrences with no I-131 uptake than in I-131-positive cases. They are correlated with the ability to concentrate F-18-FDG, and they can appear, albeit rarely, as a de novo event in the course of PTC recurrences.