Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas

Issa, Peter P.; Omar, Mahmoud; Buti, Yusef; Issa, Chad P.; Carnabatu, Christopher J.; Munshi, Ruhul; Hussein, Mohammad; Aboueisha, Mohamed; Shama, Mohamed; Corsetti, Ralph L.; Toraih, Eman A.; Kandil, Emad

doi:10.3390/biomedicines10082051

Cited by 11 publications

(16 citation statements)

References 42 publications

(50 reference statements)

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“…Numerous works have found BRAF V600E mutation to be associated with a worse initial presentation [ 49 , 50 ]. Our results found that tumors with BRAF V600E mutation were almost twice as likely (RR = 1.79) as those with BRAF wild-type PTMC to develop ETE.…”

Section: Discussionmentioning

confidence: 99%

Association of BRAFV600E Mutation with the Aggressive Behavior of Papillary Thyroid Microcarcinoma: A Meta-Analysis of 33 Studies

Attia

Hussein

Issa

et al. 2022

IJMS

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An association between the BRAFV600E mutation and the clinicopathological progression of papillary thyroid microcarcinoma (PTMC) has been suggested. We aimed to summarize the relevant literature and determine the predictive value of BRAFV600E mutation in predicting clinical outcomes and risk stratification in patients with PTMC. A systematic search using PubMed, Cochrane, and Embase up to February 2020 was performed. A total of 33 studies met the inclusion criteria, resulting in a pool of 8838 patients, of whom 5043 (57.1%) patients were positive for BRAFV600E mutation. Tumors with positive BRAFV600E mutation had a higher tendency for multifocality (RR = 1.09, 95%CI = 1.03–1.16), extrathyroidal extension (RR = 1.79, 95%CI = 1.37–2.32), and lymph node metastasis (RR = 1.43, 95%CI = 1.19–1.71). Patients with BRAFV600E mutation were at increased risk of disease recurrence (RR = 1.90, 95%CI = 1.43–2.53). PTMC in patients positive for the BRAFV600E mutation is more aggressive than wild-type BRAF PTMC. Since BRAF-mutated PTMC is generally more resistant to radioiodine treatment, patients with BRAFV600E-mutated PTMC may require earlier management, such as a minimally invasive ablative intervention. Conservative management by active surveillance may be suitable for patients with wild-type BRAFV600E PTMC.

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Section: Discussionmentioning

confidence: 99%

Association of BRAFV600E Mutation with the Aggressive Behavior of Papillary Thyroid Microcarcinoma: A Meta-Analysis of 33 Studies

Attia

Hussein

Issa

et al. 2022

IJMS

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“… 43 In addition, BRAF V600E mutation was associated with lymph node metastasis of PTMC, however the proportion of lymph node metastasis in PTMC patients with BRAF V600E mutation and Hashimoto’s thyroiditis is significantly reduced. 44 Moreover, BRAF V600E mutation was not associated with lymph node metastasis of PTMC. 45–48 Younger age (<55 years old) was an independent risk factor for lymph node metastasis in PTMC in this study.…”

Section: Discussionmentioning

confidence: 92%

Younger Than 55 Years Old and BRAF V600E Mutation are Risk Factors for Lymph Node Metastasis in Papillary Thyroid Carcinomas ≤1.0 cm but Not in >1.0 cm

Lai¹,

Gu²,

Yu³

et al. 2023

IJGM

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Background Studies on the relationship between BRAF V600E mutation and the clinicopathologic features of papillary thyroid carcinoma (PTC), risk of lymph node metastasis in papillary thyroid microcarcinoma (PTMC) have shown inconsistent results. Methods In this retrospective analysis, clinicopathological data of the patients were collected, and molecular testing was done for BRAF V600E mutation. PTC patients are divided into PTC≤1.0cm (PTMC) and PTC>1.0cm, and the relationship between BRAF V600E mutation and clinicopathologic features was analyzed respectively. Results Of the 520 PTC patients, 432 (83.1%) were female and 416 (80.0%) were <55 years old. BRAF V600E mutation was detected in 422 (81.2%) tumour samples of PTC. There was no significant difference in the frequency of BRAF V600E mutation between different age groups. There were 250 (48.1%) patients with PTMC and 270 (51.9%) patients with PTC>1.0cm. BRAF V600E mutation was significantly associated with bilateral cancer (23.0% vs 4.9%, P =0.005) and lymph node metastasis (61.7% vs 39.0%, P =0.009) in PTMC patients, while BRAF V600E mutation was significantly associated with bilateral cancer (24.9% vs 12.3%, P =0.048) in PTC>1.0cm patients. Logistic regression analysis showed that, after adjusting for gender, Hashimoto’s thyroiditis and calcification, we found that younger age (<55 years old) (OR: 2.384, 95% CI: 1.241–4.579, P =0.009) and BRAF V600E mutation (OR: 2.213, 95% CI: 1.085–4.512, P =0.029) were significantly associated with lymph node metastasis in PTMC, similar results were not obtained in PTC>1.0cm. Conclusion Younger age (<55 years old) and BRAF V600E mutation was independent risk factor for lymph node metastasis in PTMC.

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“…HT is the most common reason for hypothyroidism and is an autoimmune disease associated with chronic inflammation. Though works have suggested BRAF mutation as a risk factor for tumor aggressiveness and HT as a protective factor against tumor aggressiveness, few works have investigated the two simultaneously [ 11 , 17 ]. One potential explanation for the protective effect of HT, however, is the increased medical attention these patients already receive, and consequently, the detection of carcinomas earlier.…”

Section: Discussionmentioning

confidence: 99%

Hashimoto’s Thyroiditis: A Protective Factor against Recurrence in BRAF-Wild Type Differentiated Thyroid Carcinoma

Issa

Omar

Buti

et al. 2023

Cancers

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A recent work analyzing the concomitant factors BRAF mutation (risk factor) and Hashimoto’s thyroiditis (HT) (protective factor) found that the presence of HT reduced lymph node metastasis in BRAF-mutated papillary thyroid carcinoma. Whether this notion is upheld with respect to disease recurrence and differentiated thyroid carcinoma (DTC), however, is unknown. We aimed to investigate the effect of underlying HT in DTC patients and its influence on recurrence with a specific emphasis in BRAF-mutated tumors. A total of 469 patients were included. Patients were stratified according to BRAF and HT status. Multivariate regression analysis was conducted to determine protective and risk factors of disease recurrence in patients with DTC. HT was associated with less-aggressive carcinomas including more frequent microcarcinomas (HT: 45.0% vs. no-HT: 34.0%, p = 0.02), less lymph node involvement (HT: 16.4% vs. no-HT: 26.1%, p = 0.02), and less disease recurrence (HT: 2.9% vs. no-HT: 11.9%, p = 0.002). BRAF mutation was also significantly associated with higher rates of lymph node involvement (BRAF-mutant: 41.9% vs. BRAF-wild type: 14.6%, p < 0.001) and almost two times the rate of recurrence (BRAF-mutant: 14.9% vs. BRAF-wild type: 6.5%, p = 0.004). Underlying HT was the only protective factor determined, reducing the odds of developing recurrence by 70% (HR: 0.30, 95%CI: 0.11–0.88). In the BRAF-wild type cohort, regression analysis continued to determine HT as a protective factor (p = 0.03). However, in the BRAF-mutant cohort, HT was no longer an independent protective factor (p = 0.20) against recurrence. Sub-group regression analysis, including PTC patients, similarly found HT as a protective factor only in BRAF-wild type patients (p = 0.039) and not BRAF-mutant (p = 0.627). The presence of underlying HT is associated with less aggressive tumors and is an independent protective factor against DTC recurrence, reducing the risk by 70%. HT remains a protective factor in BRAF-wild type carcinoma, but not in patients with BRAF-mutant carcinoma. HT may potentially be considered as a parameter which enhances American Thyroid Association patient risk stratification.

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Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas

Cited by 11 publications

References 42 publications

Association of BRAFV600E Mutation with the Aggressive Behavior of Papillary Thyroid Microcarcinoma: A Meta-Analysis of 33 Studies

Association of BRAFV600E Mutation with the Aggressive Behavior of Papillary Thyroid Microcarcinoma: A Meta-Analysis of 33 Studies

Younger Than 55 Years Old and BRAF V600E Mutation are Risk Factors for Lymph Node Metastasis in Papillary Thyroid Carcinomas ≤1.0 cm but Not in >1.0 cm

Hashimoto’s Thyroiditis: A Protective Factor against Recurrence in BRAF-Wild Type Differentiated Thyroid Carcinoma

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