&lt;i&gt;BRAF&lt;/i&gt; and &lt;i&gt;TERT&lt;/i&gt; promoter mutations: clinical application in thyroid cancer

Chung, Jae Hoon

doi:10.1507/endocrj.ej20-0063

Cited by 26 publications

(18 citation statements)

References 96 publications

(110 reference statements)

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“…In the subgroup analysis, initial distant metastasis did not show a bimodal peak but showed an inverse relationship according to preoperative TSH decile in patients older than 55 years. In a recent study, initial distant metastasis in elderly patients showed a high probability of telomerase reverse transcriptase ( TERT ) promoter mutations 29 , 30 . Therefore, through the results indicating that initial distant metastasis does not increase when TSH is high in elderly patients over 55 years of age, it can be postulated that the cancer cells of older patients are highly undifferentiated owing to the mutations, and therefore the growth stimulation caused by TSH is reduced.…”

Section: Discussionmentioning

confidence: 99%

Pattern analysis for prognosis of differentiated thyroid cancer according to preoperative serum thyrotropin levels

Kim

Jung

Cho

et al. 2021

Sci Rep

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Serum thyrotropin (TSH) level after thyroid surgery affects the prognosis of differentiated thyroid cancer (DTC). However, the effects of preoperative serum TSH levels on the prognosis of DTC remain contradictory. In this study, to better understand the relationship between preoperative TSH levels and the prognosis of DTC, we performed pattern analysis of prognostic factors of DTC according to preoperative serum TSH levels. We retrospectively reviewed the clinical records of patients who were diagnosed and treated for DTC at the Samsung Medical Center, between 1994 and 2016. We reviewed preoperative serum TSH levels and performed a pattern analysis with prognostic risk factors for DTC. For pattern analysis, TSH was divided into 10 groups of equal fractions (TSH decile). We found a linear association between preoperative TSH levels and extra-thyroidal extension and lymph node metastasis. However, primary tumor size and initial distant metastasis showed a bimodal peak, which was similar to the pattern of overall and disease-specific death. We found that preoperative TSH range which showed the lowest mortality rate was about 0.8 to 1.59 mIU/L, which are slightly lower normal TSH levels. Although there was no linear trend, the primary tumor size, initial distant metastasis, and mortality of DTC were closely related with preoperative TSH decile and they showed a bimodal pattern. The results obtained in this study provide additional information for understanding the association between preoperative TSH levels and DTC prognosis.

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Section: Discussionmentioning

confidence: 99%

Pattern analysis for prognosis of differentiated thyroid cancer according to preoperative serum thyrotropin levels

Kim

Jung

Cho

et al. 2021

Sci Rep

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“…On the contrary, the most common genetic mutation in malignant thyroid cancer is BRAF. BRAF mutation is associated with higher levels of lymph node invasion, metastasis and mortality in papillary thyroid cancer 29–31 . BRAF mutation is however more sensitive than specific in determining patient mortality, as seen by the high population prevalence of BRAF compared to the overall low mortality from thyroid cancer 30 .…”

Section: Discussionmentioning

confidence: 99%

Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real‐world setting

Torrecillas

Sharma

Neuberger

et al. 2021

Clinical Endocrinology

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Objective American Thyroid Association (ATAn) 2015 guidelines recommend repeat fine‐needle aspiration with molecular marker profiling (MMP) or diagnostic lobectomy in thyroid nodules yielding atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology. Our objective is to describe the molecular profiles and histological correlates of these cytologically indeterminate nodules (CIN) to aid risk stratification. Design Retrospective chart review. Patients Adults with CIN that underwent MMP from 2017 to 2020. Measurements Pearsons' χ2, Fisher's exact test, nonparametric testing and multiple regression analysis were performed. Results A total of 89 CIN underwent mutational analysis. Of 55% (n = 49) were Bethesda class III AUS/FLUS and 45% (n = 40) were Bethesda class IV FN/SFN. The US phenotype of a CIN was isoechoic (53%) or hypoechoic (32%) with well‐defined margins (98%), absence of calcifications (75%) and mildly increased internal vascularity (70%). A total of 84% and 87% of nodules were classified as mild/moderate or low/intermediate risk per the Thyroid Imaging Reporting and Data System and ATA classifications, respectively. Based on the Thyroseq patient management resource, 6.7% (n = 6) of nodules had a high predicted probability of cancer (≥95%), 41.6% (n = 37) were intermediate probability (40%–94%) and 51.7% (n = 46) were low probability (<40%). MMP revealed positive mutations in 45% (n = 40) of nodules, with 71% demonstrating RAS mutations. Of the nodules that underwent resection (n = 38), 39% (n = 15) had malignant pathology. Increasing the threshold to recommend surgical resection to a Thyroseq predicted probability of cancer to ≥50%, had a 100% sensitivity and 65% specificity for detecting malignant nodules (area under the ROC curve: 0.86). The positive predictive value was 37% and the negative predictive value was 100%. Conclusion US phenotypes of CIN nodules were variable and did not aid in differentiating malignant from benign nodules. Of the CIN nodules with a positive MMP, most were RAS and had a benign pathology. With the exception of high‐risk genetic markers for malignancy, the threshold to recommend surgical resection should be raised for CIN. Further studies to improve risk stratification in these nodules are required.

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“…This updated and comprehensive meta-analysis demonstrates that a BRAF mutation does not increase the risk of recurrences in patients with PTC. BRAF mutations were first found in human cancers in 2002, and over 40 kinds of BRAF mutations have been identified since then [32]. The BRAF V600E mutation is the most frequent and specific genetic alteration found in PTC, which activates the tumorigenic mitogen-activated protein kinase signaling pathway [33,34].…”

Section: Discussionmentioning

confidence: 99%

The Impact of BRAF Mutation on the Recurrence of Papillary Thyroid Carcinoma: A Meta-Analysis

Kwon

2020

Cancers

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Previous meta-analyses indicated that the BRAF V600E mutation was associated with an increased recurrence rate of papillary thyroid carcinoma (PTC). However, with recent publications of large cohort studies, the need for an updated meta-analysis increases. Therefore, we conducted a comprehensive meta-analysis to assess the impact of the BRAF V600E mutation on PTC recurrences. We performed a literature search using PubMed, SCOPUS, the Cochrane Database of Systematic Reviews, and the Web of Science Core Collection, from their inception to May 31, 2020. The relevant studies compared recurrence rates using the hazard ratio (HR) of BRAF mutations; 11 studies comprising 4674 patients were identified and included. Recurrence rates in patients with the BRAF V600E mutation were comparable with BRAF wild-type patients (HR 1.16, 95% CI 0.78–1.71), after adjustment for possible confounders. In subgroup analysis, both geographical region (HRs for America, Asia, and Europe were 2.16, 1.31 and 0.66, respectively) and tumor stage (HRs for stage I and II were 1.51 and 4.45, respectively) can affect the HRs of the BRAF mutation for recurrence. In conclusion, the BRAF mutation does not increase the risk of recurrences in patients with PTC. Differences in the geographical region or tumor stage should be considered when interpreting the impact of a BRAF mutation on recurrence.

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<i>BRAF</i> and <i>TERT</i> promoter mutations: clinical application in thyroid cancer

Cited by 26 publications

References 96 publications

Pattern analysis for prognosis of differentiated thyroid cancer according to preoperative serum thyrotropin levels

Pattern analysis for prognosis of differentiated thyroid cancer according to preoperative serum thyrotropin levels

Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real‐world setting

The Impact of BRAF Mutation on the Recurrence of Papillary Thyroid Carcinoma: A Meta-Analysis

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