Combined expression of the BRAFV600E mutation and PD-L1 in early papillary thyroid carcinoma and its relationship with clinicopathological features and recurrence—a retrospective cohort study

Abstract

Background: Identifying the high recurrence group of patients with early-stage papillary thyroid cancer (PTC) is the greatest challenge in the management of this disease. It has been noted that B-type Rafkinase (BRAF) V600E mutation and programmed death ligand 1 (PD-L1) are associated in PTC and highly expressed in PTC, correlating in PTC as potential prognostic biomarkers. However, whether they can be used to predict the aggressiveness and recurrence of early PTC remains unclear. Methods: Clinicopathological data of 137 patients with early PTC [tumor-node-metastasis (TNM) stage I-II] who underwent surgery in Zhejiang Cancer Hospital between 2008 and 2010 were retrospectively analyzed. BRAF V600E mutation and PD-L1 was detected by immunohistochemistry. The median follow-up time was 136 months (interquartile range 5.8). The presence of tumor confirmed by imaging or pathology or lymph node metastasis was considered as tumor recurrence. The association of both alone and in combination with clinicopathological features and recurrence was statistically analyzed respectively. The risk of recurrence was assessed using Cox regression models. Results: Most of the 137 early PTC were female (78.1%). The mean age was 43.2±12.1 years. The median tumor size was 1.4 cm; 14 patients developed recurrence during follow-up period; 56 patients (40.9%) were detected positive for BRAF V600E mutation; 76 patients (55.5%) were detected positive for PD-L1. Patients with both BRAF V600E mutation and PD-L1 expression had larger tumors (P=0.038), were more likely to have extrathyroidal invasion (P=0.045), and had a lower rate of cervical lymph node metastasis (P=0.046). The recurrence rate was 17.5% (7/40) in patients with BRAF V600E mutation and PD-L1 double expression compared to 8.9% (4/45) in patients with BRAF V600E mutation and PD-L1 double negative [hazard ratio (HR) =1.267; 95% CI: 0.841-1.909; P=0.257]. Survival curves showed flatter recurrence-free survival (RFS) curves in positive BRAF V600E mutation only and PD-L1 expression only, whereas decreased sharply in positive ^ ORCID: 0000-0002-9275-0858.

Characteristics and immune checkpoint status of radioiodine-refractory recurrent papillary thyroid carcinomas from Ukrainian Chornobyl Tissue Bank donors

“…It should be noted that in contrast to other studies ( 51 , 52 ), we did not find an association between positive ICS and the BRAF V600E mutation. A high frequency of BRAF V600E -positive RAI-R recurrent PTCs (approximately 70%) was found regardless of their ICS.…”

Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies

“…Interestingly, this discrepancy is further compounded by the fact that many PTCs have BRAF mutations and also express CD274. 31 32 Therefore, we sought to investigate the significance of BRAF mutation and its downstream signaling on the expression of immune suppressive markers in PTC tissues. Further, we explore the efficacy of BRAF inhibitors in combination with immunotherapy.…”

Clinical characteristics of primary parathyroid adenoma and its relationship with coexisting papillary thyroid carcinoma: a clinical retrospective study

“…Hu et al found that PTC showed more malignant pathological features and early recurrence in patients with changes in internal environment (such as solid organ transplantation) ( 21 , 22 ). Beebeejaun et al speculated the interaction mechanism of PA and PTC in his article, high PTH level, Hypercalcemia and low 1,25 Dihydroxyvitamin D may lead to the growth and aggressivity of PTC ( 23 ).…”