Seven-year follow-up of a juvenile female with papillary thyroid carcinoma with poor outcome, BRAF mutation and loss of expression of iodine-metabolizing genes

Abstract

Background: Recent studies reported that BRAF V600E mutation, the most prevalent genetic event found in papillary thyroid carcinoma, is an independent poor prognostic marker. Additionally, it correlates with a less differentiated tumor stage due to reduced expression of key genes involved in iodine metabolism. We previously described a patient with BRAF V600E mutation in primary tumor and a new mutation (V600E+K601del) in the matched-lymph node metastases. In the present study we report an unusual clinical behavior of PTC and correlate with BRAF mutational status and level of expression of TSHR and NIS. Methods: Quantitative PCR (qPCR) was used to evaluate the NIS and TSHR level of expression in matched papillary thyroid carcinoma and adjacent normal tissue. Results: In this study, we presented a seven-year follow up of a juvenile papillary thyroid carcinoma patient who had an aggressive tumor harboring BRAF mutation, and failed to conventional therapy. We found a markedly decrease of NIS and TSHR expression in primary PTC compared to adjacent normal thyroid tissue. Conclusion: Our fi ndings suggest that BRAF mutational status and decreased NIS and TSHR expression in this patient may reduce radioiodine uptake and lead to a negative response to radioiodine therapy.

Cytotoxic and genotoxic effects of 131I and 60Co in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid‐stimulating hormone treatment

“…We do not have a full explanation for the observed data. However, the need for a higher extracellular level of radioiodine for a significant uptake, which would be higher than the ablative activity of 13I I normally used in DTC patients can be suggested [Rudavsky and Freeman, , Oler et al, , Ferrari et al, ]. Thus, it is possible that such high activity of 131 I, could promote an up‐regulation of thyroid‐specific gene expression, responsible for iodine metabolism in thyroid cancer cells carrying the BRAF mutation, which can be potentialized by TSH.…”

“…External irradiation with 60 Co gamma rays, characterized by their high penetration power, as a coadjutant for radioiodine therapy is also a possibility, but further studies are needed to take into consideration the relatively high radioiodine activity, of the order of 500 mCi/patient, necessary to permit adequate 131 I incorporation. These data confirm those reported by Rudavsky and Freeman [] and Oler et al [], who found that selective 131 I uptake occurred only at the highest administered activity of 515 and 450 mCi, respectively.…”

Mutação BRAF em pacientes idosos submetidos à tireoidectomia

“…The association between the classic variant of papillary carcinoma and BRAF mutation with a more aggressive phenotype due to reduced expression of iodinemetabolizer genes suggests the detection of BRAF mutation as a prognostic factor, an assistant in therapy choice for patients with papillary carcinoma 23 . It is believed that the papillary carcinomas with BRAF mutation may have lower uptake of iodine in the postoperative period, which translates into more aggressive phenotype and a higher chance of recurrence 15,29,30 , indicating that in these cases, at least the follow-up must be strict.…”

“…The association between the classic variant of papillary carcinoma and BRAF mutation with a more aggressive phenotype due to reduced expression of iodinemetabolizer genes suggests the detection of BRAF mutation as a prognostic factor, an assistant in therapy choice for patients with papillary carcinoma 23 . It is believed that the papillary carcinomas with BRAF mutation may have lower uptake of iodine in the postoperative period, which translates into more aggressive phenotype and a higher chance of recurrence 15,29,30 , indicating that in these cases, at least the follow-up must be strict.Elisei et al published the first series of cases with consistent follow-up to suggest that BRAF mutation is associated with poor prognosis and appears to be a factor independent from age 25 . In 102 patients with papillary carcinoma and mean follow up of 15 years, the mutation frequency was 37.3%, but was higher in patients over 60 years of age, which confirms the data found in this study.…”