BRAF mutation positive papillary thyroid carcinoma is less advanced when Hashimoto's thyroiditis lymphocytic infiltration is present.

Concomitant papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) is a frequent occurrence. Whether these two conditions are linked and whether PTC with concurrent HT has distinct clinicopathological characteristics are still debated issues. Lymphocytic infiltration is abundant in HT and might be relevant in the pathogenesis and progression of PTC. BRAF(V600E) mutation is associated with a more advanced PTC at diagnosis; however, its role in the clinicopathological characteristics of PTC with concurrent HT is unknown. We enrolled 146 patients with histological diagnosis of PTC. Microscopic assessment of histology samples was performed to identify the presence of lymphocytic infiltration. Detection of BRAF(V600E) was performed on cytology samples by both direct sequencing and pyrosequencing, and results were correlated with clinical parameters. Concurrent HT lymphocytic infiltration was associated with the female gender, smaller tumour size, a less frequent extracapsular extension and a lower grade of TNM staging. BRAF(V600E) was more frequent in PTC with concomitant lymphocytic infiltration. In PTC harbouring BRAF(V600E) , concurrent lymphocytic infiltration was still associated with the female gender, a less frequent extracapsular extension and a lower TNM staging. These results suggest that lymphocytic infiltration of HT is a protective factor against PTC progression, and it is independent of BRAF mutational status.

Marotta V ，Guerra A ，Zatelli MC ，Uberti ED ，Di Stasi V ，Faggiano A ，Colao A ，Vitale M ... -  《-》

Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer.

The purpose of this study was to evaluate the association between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid cancer (PTC) and to determine their combined association with tumor aggressiveness in PTC. A total of 1780 patients with PTC who underwent surgery were enrolled in this study. Simple and multiple analyses were performed to determine the association between Hashimoto's thyroiditis and the BRAF(V600E) mutation in PTC. Hashimoto's thyroiditis was present in 11.5% of patients (204/1780) with PTC. Multiple logistic regressions showed that BRAF(V600E) (odds ratio [OR] = 0.493; 95% confidence interval [CI] = 0.360-0.678) and the female sex (OR = 7.146; 95% CI = 3.408-18.347) were independent factors associated with Hashimoto's thyroiditis in PTC. BRAF(V600E) mutation and the Hashimoto's thyroiditis-negative PTC group were associated with aggressive disease (OR = 3.069; 95% CI = 1.654-5.916). Hashimoto's thyroiditis was associated less frequently with BRAF(V600E) , and frequently with the female sex in patients with PTC. Hashimoto's thyroiditis and BRAF(V600E) status may help to predict clinical outcome of PTC.

Kim SJ ，Myong JP ，Jee HG ，Chai YJ ，Choi JY ，Min HS ，Lee KE ，Youn YK ... -  《-》

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma.

It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (OR=0.662, P=0.023) and BRAF-positive (OR=0.817, P=0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (OR=0.675, P=0.044) and BRAF-positive (OR=0.817, P=0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status.

Kim SK ，Woo JW ，Lee JH ，Park I ，Choe JH ，Kim JH ，Kim JS ... -  《-》

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF(V600E) mutation.

Diffuse lymphocytic infiltration (DLI) is frequently found with papillary thyroid cancer (PTC), so there has been long interest in how it affects the characteristics of PTC. This purpose of this study was to define the association between DLI and PTC aggressiveness according to thyroperoxidase antibody (TPOAb) and B-type Raf (BRAF)V600E mutation positivity. There were 1879 patients with PTC who underwent surgery and were enrolled in this study. Clinicopathologic characteristics were compared between groups according to the presence of DLI and TPOAb. Multiple logistic regression analysis was conducted to assess odds ratio (OR) for each dependent variable (BRAFV600E mutation, tumor size >1.0 cm, multifocality, extrathyroidal extension, and lymph node metastasis) of each group according to the presence of DLI and TPOAb, with the group with neither DLI or TPOAb (DLI-negative TPOAb-negative PTC) as the reference. The DLI-positive PTC showed more frequent multifocality and less frequent BRAFV600E mutation than DLI-negative PTC. Among patients with DLI-positive PTC, extrathyroidal extension and BRAFV600E mutation was less frequent when serum TPOAb was positive. In multiple logistic regressions, DLI-positive TPOAb-positive PTC showed a high OR for multifocality (1.410; P = .017), but low ORs for BRAFV600E mutation (0.521; P < .001) and extrathyroidal extension (0.691; P = .008). The patients with DLI-positive TPOAb-positive PTCs showed a high OR for multifocality (1.588; P = .002), and high ORs for tumor size >1.0 cm (2.205; P = .019) and lymph node metastasis (2.005; P = .032) in subgroup analyses of PTC with wild-type BRAF. The DLI-negative TPOAb-positive group was not associated with any tumor aggressiveness-related variables. Although DLI was associated with multifocality regardless of TPOAb positivity, it was associated with an indolent feature when TPOAb was positive but with aggressive features in PTC with wild-type BRAF when TPOAb was negative. The TPOAb and BRAF status may help to define the clinical implication of lymphocytic infiltration found with PTC.

Lee YK ，Park KH ，Park SH ，Kim KJ ，Shin DY ，Nam KH ，Chung WY ，Lee EJ ... -  《-》

BRAF(V600E) assessment by pyrosequencing in fine needle aspirates of thyroid nodules with concurrent Hashimoto's thyroiditis is a reliable assay.

Guerra A ，Di Stasi V ，Zeppa P ，Faggiano A ，Marotta V ，Vitale M ... -  《-》