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

Abstract

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.

Development and validation of a nomogram for preoperative prediction of ipsilateral cervical central lymph node metastasis in papillary thyroid cancer: a population-based study

“…Other studies have indicated that patients with HT present with lower aggressiveness at onset and better prognosis in PTC ( 24 , 25 ), suggesting that the chronic inflammatory environment induced by HT may limit cancer cell invasion and metastasis through enhanced local immune surveillance. A study found ( 26 ) that in PTC patients with the BRAF wild-type, the presence of HT appears to offer a more pronounced protective factor against the risk of disease recurrence, a protective effect that seems less significant in patients with BRAF mutations. Unfortunately, our study lacks genetic data, preventing stratified analysis.…”