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

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. 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. BRAFV600E 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. 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 BRAFV600E mutation; 76 patients (55.5%) were detected positive for PD-L1. Patients with both BRAFV600E 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 BRAFV600E mutation and PD-L1 double expression compared to 8.9% (4/45) in patients with BRAFV600E 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 BRAFV600E mutation only and PD-L1 expression only, whereas decreased sharply in positive expression of both BRAFV600E mutation and PD-L1; however, the differences were not significant (P>0.05). The combination of BRAFV600E mutation and PD-L1 to identify group at higher risk of recurrence in early PTC has insufficient clinical evidence and should be used with caution in the clinical management of PTC.