The synergic effect of BRAF&lt;sup&gt;V600E&lt;/sup&gt; mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma

Qu, Haijiang; Qu, Xueyan; Hu, Ze Dong; Yang, Lin; Wang, Junrong; Zheng, Chang-Fu; Tan, Zhuo

doi:10.1507/endocrj.ej17-0110

“…It was reported that tumor multifocality is not considered to be an independent risk factor of BRAF V600E mutation in PTC patients [ 30 ]. However, previous research also has demonstrated that BRAF V600E mutation is closely related to tumor multifocality with poor prognosis and aggressively behavior in PTC patients [ 31 ]. Our results showed that BRAF V600E mutation was related to multifocality in PTC patients which is analogous with previous research (OR = 1.22).…”

Section: Discussionmentioning

confidence: 99%

Risk and Prognostic Factors for BRAFV600E Mutations in Papillary Thyroid Carcinoma

Hao

¹

,

Wang

²

,

Xiong

³

et al. 2022

BioMed Research International

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Background. Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing 6% annually. PTC has become the malignant tumor with the highest growth rate in the world that fourteen PTC-related mutant genes have been identified. Whether the BRAFV600E mutation related to more aggressive clinicopathologic features and worse outcome in PTC remains variable and controversial. We aim to investigate the risk factors that may predict the BRAFV600E mutation potential of these lesions and new prevention strategies in PTC patients. Methods. A total of 9,908 papillary thyroid carcinoma patients with average 74.6% BRAFV600E mutations were analyzed (RevMan 5.3 software) in this study. The PubMed, Embase, and ISI Web of Science databases were systematically searched for works published through December 15, 2021. Results. The following variables were associated with an increased risk of BRAFV600E mutation in PTC patients: age ≥ 45 years ( OR = 1.39 , 95 % CI = 1.21 – 1.60 , p < 0.00001 ), male gender ( OR = 1.13 , 95 % CI = 0.99 – 1.28 , p = 0.06 ), multifocality ( OR = 1.22 , 95 % CI = 1.07 – 1.40 , p = 0.004 ), lymph node metastasis ( OR = 1.33 , 95 % CI = 0.79 – 2.23 , p = 0.28 ), extrathyroidal extension + ( OR = 1.61 , 95 % CI = 1.06 – 2.44 , p = 0.03 ), vascular invasion + ( OR = 2.04 , 95 % CI = 1.32 – 3.15 , p = 0.001 ), and tumor node metastasis stage ( OR = 1.61 , 95 % CI = 1.38 – 1.88 , p < 0.00001 ). In addition, tumor size (>1 cm) ( OR = 0.51 , 95 % CI = 0.32 – 0.81 , p = 0.005 ) and distant metastasis ( OR = 0.69 , 95 % CI = 0.22 – 2.21 , p = 0.54 ) had no association or risk with BRAFV600E mutation in PTC patients. Conclusion. Our systematic review identified the following significant risk factors of BRAFV600E mutation in PTC patients: age (≥45 years), gender (male), multifocality, lymph node metastasis, vascular invasion, extrathyroidal extension, and advanced tumor node metastasis stage (stages III and IV). Tumor size (>1 cm) and distant metastasis do not appear to be correlated with BRAFV600E mutation in PTC patients.

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“…Finally, 14 retrospective studies and two prospective study from 2012 to 2023 were included in our review. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Most studies were performed in Asian countries including 11 from China, two from South Korea and one from Saudi Arabia. Basic information was demonstrated in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Gene mutations as predictors of central lymph mode metastasis in cN0 PTC: A meta‐analysis

Ji,

Shi

2023

Clinical Genetics

0

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Gene mutations could predict the tumor progression and prognosis, which are us to predict CLNM in patients with cN0 PTC, however, these results are not consistent. This meta‐analysis tried to identify gene mutations which could predict CLNM in patients with cN0 PTC. A systematic search was performed for identifying relevant literature published prior to July 2023 in three search engines: PubMed, EMBASE and Web of Science. Studies that investigated the gene mutations for CLNM in patients with cN0 PTC were included in our meta‐analysis. Sixteen studies, including 6095 cN0 PTC with BRAF mutations were include in our meta‐analysis. The prevalence of CLNM in cN0 PTC ranged from 13.7% to 50.6%. The pooled analysis demonstrated that BRAFV600E mutation is significantly associated with CLNM (OR = 2.01, 95% CI: 1.55–2.60, p < 0.001) in PTC and PTMC (OR = 1.70, 95% CI: 0.51–1.81, p < 0.001). Whereas, cN0 PTC with TERT (OR = 1.94, 95% CI: 0.51–7.36, p = 0.33) and KRAS (OR = 0.57, 95% CI: 0.51–1.81, p = 0.34) mutations might not contribute to predict CLNM. Our analysis identified that BRAF mutation was a predictive factor for cN0 PTC, as well as for cN0 PTMC, which could be useful for clinician to accurately choose prophylactic CLND and better manage cN0 PTC.

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“…The potential role of BRAF mutation as a preoperative molecular marker of risk has reignited the issue. Many retrospective studies documented an association between BRAF mutation and lymph node metastases, [7][8][9][10][11][12][13][14] as well as a few prospective studies. 15 Kim et al 16 found an association only for PTC between 2 and 4 cm, as did Huang et al, 6 who proposed a TT for BRAF + solitary intrathyroidal PTC instead of a lobectomy as recommended by the American Thyroid Association guidelines.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sentinel Node Biopsy in Clinically N0, BRAF V600E–Mutated, Small Papillary Thyroid Carcinoma

Puccini

¹

,

Manca

²

,

Neri

³

et al. 2019

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Purpose: BRAF V600E mutation papillary thyroid cancer (PTC) is more aggressive with a higher risk of lymph node involvement and a poorer prognosis. Prior studies failed to demonstrate the superiority of prophylactic lymphadenectomy. We investigated the utility of additional radio-guided sentinel node biopsy (SNB). Methods: We analyzed 15 patients with N0 PTC by ultrasound and BRAF mutation on preoperative biopsy treated with total thyroidectomy (TT) or TT + prophylactic central neck dissection (PCND) alone or with SNB. Conventional surgery was performed before SNB. We recorded primary tumor diameter, multifocality, extrathyroid infiltration, neoplastic emboli, and tall cell variant. At follow-up, we evaluated basal and stimulated thyroglobulin and ultrasound or radioiodine scintigraphy. Results: Of 15 consecutive patients, 5 received conventional surgery alone, and 10 had SNB. For the first group, 4 underwent TT, and 1 had TT + PCND. Among the SNB group, 1 had no sentinel node detected and underwent a simple TT, 2 had TT + PCND+ SNB in the lateral compartment, and 7 had TT + SNB in 1 to 3 neck compartments. Micrometastases were found in 1 of 3 PCND specimens. Sentinel node biopsy revealed metastasis in 3 of 6 central compartment biopsies, in 2 of 6 biopsies in the ipsilateral lateral compartment, and in none of 2 biopsies in the contralateral compartment. Sentinel node biopsy allowed the removal of micrometastases in 4 of 10 patients. At 53 months' (mean) follow-up, no relapse was documented. Conclusions: Radio-guided SNB correctly and efficiently stages cN0 BRAF-mutated PTC patients. Sentinel node biopsy could limit timeconsuming, risk-exposing compartmental prophylactic dissections.

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The synergic effect of BRAF<sup>V600E</sup> mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma

Cited by 17 publications

References 39 publications

Risk and Prognostic Factors for BRAFV600E Mutations in Papillary Thyroid Carcinoma

Risk and Prognostic Factors for BRAFV600E Mutations in Papillary Thyroid Carcinoma

Gene mutations as predictors of central lymph mode metastasis in cN0 PTC: A meta‐analysis

Effect of Sentinel Node Biopsy in Clinically N0, BRAF V600E–Mutated, Small Papillary Thyroid Carcinoma

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