BRAF V600E and RET/PTC Promote the Activity of Nuclear Factor-κB, Inflammatory Mediators, and Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Study of 50 Patients in Inner Mongolia

Abstract

BACKGROUND The aim of this study was to investigate the expression of the BRAF V600E gene mutation and the RET/PTC gene rearrangement in the progression of papillary thyroid carcinoma (PTC) in 50 patients from Inner Mongolia. MATERIAL AND METHODS Clinical data, blood, and tissue samples were obtained from 50 patients with PTC and ten patients with benign thyroid adenoma. Expression of BRAF V600E, RET/PTC, nuclear factor-κB (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, C-X-C motif chemokine ligand (CXCL)1, CXCL2, C-C motif chemokine ligand (CCL)2, and CCL3 were measured using polymerase chain reaction (PCR), immunohistochemistry, and an enzyme-linked immunosorbent assay (ELISA). RESULTS Of the 50 patients with PTC, 37 patients expressed the BRAF V600E gene mutation, eight patients expressed RET/PTC, and five patients showed concomitant BRAF V600E and RET/PTC. Time to recurrence for patients with PTC with BRAF V600E was significantly increased compared with patients with concomitant BRAF V600E mutation and RET/PTC rearrangement (P<0.05). Expression of BRAF V600E, RET/PTC, and concomitant expression of BRAF V600E and RET/PTC were significantly associated with patient age and lymph node metastasis (P<0.05). Serum levels of NF-κB, IL-1β, IL-6, TNF-α, TGF-β and CCL3, and tumor tissue levels of IL-1β, IL-6, TNF-α, TGF-β, CXCL2 and CCL2 in patients with PTC were significantly increased compared with patients with benign thyroid adenoma, before and after surgery (P<0.05). CONCLUSIONS Expression of the BRAF V600E mutation and RET/PTC translocation promoted the activity of NF-κB, expression of inflammatory mediators, and lymph node metastases in patients with PTC.

Figure 1

Photomicrographs of the light microscopy of papillary thyroid carcinoma (PTC) and benign thyroid adenoma, routinely stained with hematoxylin and eosin (H&E) and using immunohistochemistry (IHC) for RET/PTC and nuclear factor-κB (NF-κB) (p65). (A) Tissue section showing the histological findings in papillary thyroid carcinoma (PTC). Hematoxylin and eosin (H&E). (B) Tissue section showing the histological findings in benign thyroid adenoma (TA). (H&E). (C) Immunohistochemistry shows positive immunostaining for RET/PTC in tissue from a case of papillary thyroid carcinoma (PTC). (D) Negative immunostaining for RET/PTC. (E) Immunohistochemistry shows positive immunostaining for nuclear factor-κB (NF-κB) (p65) in tissue from a case of papillary thyroid carcinoma (PTC). (F) Negative immunostaining for NF-κB.

Figure 2

Distribution of gender, age, time to recurrence, lymph node metastases, and positive expression of nuclear factor-κB (NF-κB) in patients with papillary thyroid carcinoma (PTC) and patients with benign thyroid adenoma (TA). (A) Comparison of clinical data between patients with papillary thyroid carcinoma (PTC) and patients with benign thyroid adenoma. (B) Comparison of clinical data among patients with different types of PTC. (C) Comparison of serum factors between patients with PTC and patients with benign thyroid adenoma, before and after surgery. (D) Comparison of serum factors among patients with different kinds of PTC, before and after surgery. (E) Comparison of tumor tissue factors between patients with PTC and patients with benign thyroid adenoma. (F) Comparison of tumor tissue factors among patients with different kinds of PTC. * Comparing between different groups, P<0.05; ^# Comparison between male and female patients, P<0.05; ^@ Comparisons of expression of BRAF V600E, P<0.05; ^$ Comparison of expression of RET/PTC, P<0.05.