Zhang Meili, Gu Jialei, Wang Wendong, Wang Kejing, Zheng Linfeng, Feng Jianguo, Shang Jinbiao
The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Thyroid Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Gland Surg. 2022 Dec;11(12):1908-1923. doi: 10.21037/gs-22-701.
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. 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 mutation; 76 patients (55.5%) were detected positive for PD-L1. Patients with both 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 mutation and PD-L1 double expression compared to 8.9% (4/45) in patients with 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 mutation only and PD-L1 expression only, whereas decreased sharply in positive expression of both mutation and PD-L1; however, the differences were not significant (P>0.05).
The combination of 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.
识别早期甲状腺乳头状癌（PTC）患者的高复发组是该疾病管理中最大的挑战。已经注意到，B型 Raf激酶（BRAF）V600E突变与程序性死亡配体1（PD-L1）在PTC中相关联且在PTC中高表达，在PTC中作为潜在的预后生物标志物相互关联。然而，它们是否可用于预测早期PTC的侵袭性和复发仍不清楚。
回顾性分析了2008年至2010年期间在浙江省肿瘤医院接受手术的137例早期PTC患者[肿瘤-淋巴结-转移（TNM）分期I-II期]的临床病理数据。通过免疫组织化学检测BRAF V600E突变和PD-L1。中位随访时间为136个月（四分位间距5.8）。通过影像学或病理学证实的肿瘤存在或淋巴结转移被视为肿瘤复发。分别对BRAF V600E突变和PD-L1单独及联合临床病理特征与复发的关联进行统计学分析。使用Cox回归模型评估复发风险。
137例早期PTC患者中大多数为女性（78.1%）。平均年龄为43.2±12.1岁。肿瘤中位大小为1.4 cm；14例患者在随访期间出现复发；56例患者（40.9%）BRAF V600E突变检测为阳性；76例患者（55.5%）PD-L1检测为阳性。BRAF V600E突变和PD-L1表达均阳性的患者肿瘤更大（P = 0.038），更易发生甲状腺外侵犯（P = 0.045），且颈部淋巴结转移率较低（P = 0.046）。BRAF V600E突变和PD-L1双表达患者的复发率为17.5%（7/40），而BRAF V600E突变和PD-L1双阴性患者的复发率为8.9%（4/45）[风险比（HR）= 1.267；95%置信区间：0.841 - 1.909；P = 0.257]。生存曲线显示，仅BRAF V600E突变阳性和仅PD-L1表达阳性时无复发生存（RFS）曲线较平缓，而BRAF V600E突变和PD-L1表达均阳性时曲线急剧下降；然而，差异无统计学意义（P>0.05）。
BRAF V600E突变和PD-L1联合用于识别早期PTC中复发风险较高的组缺乏充分的临床证据，在PTC的临床管理中应谨慎使用。
