BRAF in primary and recurrent papillary thyroid cancers: the relationship with (131)I and 2-[(18)F]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 ((131)I) uptake are frequently associated with BRAF mutations, a low expression of thyroid-related genes and a high expression of glucose type-1 transporter gene.


OBJECTIVE
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 (131)I and/or 2-[(18)F]fluoro-2-deoxi-d-glucose ((18)F-FDG) in the recurrent cancers, serum markers of recurrence, and patient outcome.


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 (18)F-FDG-positron emission tomography-computed tomography.


RESULTS
BRAF V600E-positive recurrent patients were found (131)I-negative in 94% of cases (P<0.001); 73% of the cancers carrying BRAF V600E were both (131)I-negative and (18)F-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 (131)I-negative and BRAF V600E-positive recurrent cancers deceased during follow-up.


CONCLUSIONS
BRAF mutations are more common in thyroid recurrences with no (131)I uptake than in (131)I-positive cases. They are correlated with the ability to concentrate (18)F-FDG, and they can appear, albeit rarely, as a de novo event in the course of PTC recurrences.
Barollo
Susi
S
Istituto Oncologico Veneto - IRCCS, Padova, Italy.
Pennelli
Gianmaria
G
Vianello
Federica
F
Watutantrige Fernando
Sara
S
Negro
Isabella
I
Merante Boschin
Isabella
I
Pelizzo
Maria Rosa
MR
Rugge
Massimo
M
Mantero
Franco
F
Nacamulli
Davide
D
Girelli
Maria Elisa
ME
Busnardo
Benedetto
B
Mian
Caterina
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005838:Genotype; D006801:Humans; D007457:Iodine Radioisotopes; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D007457:Iodine Radioisotopes; D019788:Fluorodeoxyglucose F18; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf