Preoperative detection of TERT promoter and BRAFV600E mutations in papillary thyroid carcinoma in high-risk thyroid nodules

Abstract

Objectives: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAF V600E mutation. Subjects and methods: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAF V600E and pTERT mutations. Results: We found coexistence of pTERT C228T and BRAF V600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAF V600E positives. There was a significant association between pTERT C228T /BRAF V600E with older age and advanced stage compared with the group negative for either mutation. Conclusions: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERT C228T /BRAF V600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.

The Coexistence of Genetic Mutations in Thyroid Carcinoma Predicts Histopathological Factors Associated With a Poor Prognosis: A Systematic Review and Network Meta-Analysis

“…Of the eight outcomes (primary outcomes: lymph node metastasis, disease stage, distant metastatis, and extrathyroidal extension; and secondary outcomes: tumor recurrence, mortality, invasion of the thyroid capsule, and multiplicity) analyzed, the coexistent BRAF V600E + TERT mutation ranked highest five times ( Table 2), demonstrating that it has a profound impact on the histopathological features associated with a worse prognosis. Giorgenon et al documented a significant association between the dual TERTp/BRAF V600E mutation and advanced stage, compared with the control group that was negative for two mutations (33), consistent with our results. Kim and colleagues concluded that, compared with the presence of a single mutation, concomitant TERT and BRAF mutations worsened the survival rate of papillary cancer patients (57).…”

“…In such cases, it is possible that the no mutation group actually included other kinds of mutations, which may have a certain impact on the overall results. What's more, AJCC staging system 8 th edition begins to be used internationally from Jan 2019, and only two studies using the new edition AJCC staging system (32,33), which maybe also a limitation of our research. Last but not least, we were only able to select 21 studies relating to PTC, and were therefore limited by patient numbers.…”

“…Table 2 show the network meta-analysis results for the primary outcomes, including disease stage, lymph node metastasis, extrathyroidal extension, and distant metastasis. In the evaluation of disease stage ( 32 , 33 , 36 – 39 , 44 , 45 , 47 – 56 ), incorporated nine active mutant arms from 18 of the selected studies. Compared with wild-type, BRAF V6000E + TERT mutations ranked highest with significant differences (OR = 5.74, 95% CrI: 3.09–10.66), followed by BRAF V6000E + CHEK2 (10.66, 2.10–54.11), TERT + RAS , BRAF V6000E + RET/PTC , TERT , RET/PTC , BRAF V6000E , CHEK2 , and RAS .…”

Thyroid Nodule Molecular Testing: Is It Ready for Prime Time?

“…Ultimately, given our increasing understanding of thyroid cancer biology, molecular testing needs to become more precise and directed specifically toward informing what therapy to offer once thyroid cancer is diagnosed, [such as by the identification of actionable RET, NRTK, BRAF, VEGFR mutations, and pathway alterations that would allow for the use of targeted agents ( 61 – 64 )]. For instance, there are exciting advanced being made in the research setting on development of new molecular markers (e.g., TERT expression) that can improve prognostication and treatment of thyroid cancer ( 65 ).…”

Value of pyruvate carboxylase in thyroid fine-needle aspiration wash-out fluid for predicting PTC lymph node metastasis

“…Although BRAF V600E and TERT C228T mutations are widely tested in the clinic, 40% of DTCs with distant metastases show negative BRAF or TERT genetic mutation (33). Liu et al (34) found that the TERT C228T mutation and the BRAF V600E mutation led to dedifferentiation and aggressive biological behavior of thyroid cancer (35). However, the probability of the BRAF V600E and TERT C228T mutations occurring simultaneously in PTC is 13% (36).…”