Association Between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma
Association Between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma
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甲状腺髓样癌中程序性死亡配体 1 表达与临床病理特征、结构性复发和生化复发/持续性疾病之间的关联
DOI：
10.1089/thy.2019.0079
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发表时间：
2019-08-19
期刊：
影响因子：
6.6
通讯作者：
Ji, Qing-Hai
中科院分区：
文献类型：
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作者：
Shi, Xiao;Yu, Peng-Cheng;Ji, Qing-Hai
背景：程序性死亡配体1(PD-L1)在甲状腺髓样癌(MTC)中的表达鲜有报道。在本研究中，我们评估了PD-L1在MTC中的阳性表达，并分析了其与临床病理特征、结构性复发(SR)和生化复发/持续性疾病(BCR/BCPD)的相关性。我们还评估了PD-L1在发生远处或无法切除的局部复发患者中的表达情况。方法：纳入2006-01-2015-12在我科接受首次手术的连续201例MTC患者。采用免疫组织化学方法检测PD-L1的表达，若联合评分<gt；=1则认为PD-L1阳性。回顾分析PD-L1表达与临床病理特征、结构无复发生存期(SRFS)和BCR/BCPD的关系。结果：整个队列的中位随访期为73个月。我们观察到29例(14.4%)患者PD-L1染色阳性，这些患者肿瘤较大(p=0.002)，有淋巴结转移(p=0.036)，分期较晚(p=0.019)。PD-L1阴性组和PD-L1阳性组的5年生存率分别为85.4%和57.9%(p=0.001)。多变量COX分析显示PD-L1阳性与SR独立相关(危险比=2.19[95%可信区间(CI)1.01-4.77]，p=0.047)。多因素Logistic回归分析显示PD-L1阳性与BCR/BCPD显著相关(优势比=3.16[CI1.16~8.66]，p=0.025)。在研究期间，20名患者发生了远处或无法切除的局部复发，其中8名(40%)PD-L1阳性，远远高于整个MTC人群。结论：利用一大群MTC患者，我们证明PD-L1阳性与侵袭性临床病理特征相关，并独立预测SR和BCR/BCPD。此外，在不可治愈的复发患者中观察到PD-L1的高表达。因此，针对程序性细胞死亡-1(PD-1)/PD-L1通路的免疫检查点抑制剂可能是治疗晚期MTC的一种潜在的治疗策略。
Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score >= 1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.