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

Abstract

ObjectiveBRAF 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 (131I) uptake are frequently associated with BRAF mutations, a low expression of thyroid-related genes and a high expression of glucose type-1 transporter gene.AimThe 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 131I and/or 2-[18F]fluoro-2-deoxi-d-glucose (18F-FDG) in the recurrent cancers, serum markers of recurrence, and patient outcome.Design and methodsWe 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 18F-FDG-positron emission tomography–computed tomography.ResultsBRAF V600E-positive recurrent patients were found 131I-negative in 94% of cases (P<0.001); 73% of the cancers carrying BRAF V600E were both 131I-negative and 18F-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 131I-negative and BRAF V600E-positive recurrent cancers deceased during follow-up.ConclusionsBRAF mutations are more common in thyroid recurrences with no 131I uptake than in 131I-positive cases. They are correlated with the ability to concentrate 18F-FDG, and they can appear, albeit rarely, as a de novo event in the course of PTC recurrences.