程序性细胞死亡配体1在甲状腺乳头状癌合并桥本甲状腺炎中的表达及其临床意义

Expression of programmed cell death ligand 1 in papillary thyroid carcinoma with coexistent Hashimoto’s thyroiditis and its clinical significances

目的检测程序性细胞死亡配体1(PD-L1)在甲状腺乳头状癌(PTC)及其合并桥本甲状腺炎(HT)组织中的表达情况并探讨其表达的临床意义。方法回顾性收集2017年3月至2019年5月期间在贵州医科大学附属医院甲状腺外科接受甲状腺切除术的PTC患者。采用免疫组织化学染色法检测PD-L1蛋白在PTC组织中的表达情况,PD-L1染色阳性细胞≥20%判定为PD-L1高表达即表达阳性,<20%判定为PD-L1低表达即表达阴性;分析PD-L1蛋白表达阳性率与PTC患者临床病理特征的关系,并研究PTC患者中HT的存在与PD-L1蛋白表达的相关性。结果本研究共纳入138例PTC患者,其中单纯PTC者104例,合并HT的PTC者34例。PD-L1蛋白在138例PTC组织中的表达阳性率为35.5%(49/138),其中在单纯PTC组织中为43.3%(45/104),在合并HT的PTC组织中为11.8%(4/34),后者明显低于前者(P=0.001)。单因素分析结果显示,PD-L1蛋白表达阳性率与PTC患者的肿瘤大小、有无腺外侵犯及是否合并HT有关(P<0.05),且Spearman等级相关分析结果发现PD-L1表达与肿瘤大小(r_(s)=0.173,P=0.041)和腺外侵犯(r_(s)=0.197,P=0.021)呈正相关、与是否合并TH呈负相关(r_(s)=–0.284,P=0.001);对这3个因素进一步进行二元logistic回归多因素分析结果显示,PD-L1蛋白表达阳性率与PTC是否合并HT密切相关[OR=5.720,95%CI(1.879,17.411),P=0.002],未发现其与肿瘤大小和有无腺外侵犯有关(P>0.05)。结论PD-L1蛋白表达阳性率与PTC患者的肿瘤大小和有无腺外侵犯有一定的关系,且PD-L1在合并或不合并HT的PTC患者中的表达阳性率差异明显,即在伴HT的PTC中PD-L1表达阳性率明显降低,提示合并HT可能是PTC发生的抑制性因素,PTC的免疫微环境相关因子可能参与了甲状腺癌的发生及发展。

Objective To detect the expression of programmed cell death ligand 1(PD-L1)in papillary thyroid carcinoma(PTC)and PTC with coexistent Hashimoto’s thyroiditis(HT)tissues,and to explore its clinical significance of its expression.Methods The PTC patients who underwent thyroidectomy at the Thyroid Surgery Department of the Affiliated Hospital of Guizhou Medical University from March 2017 to May 2019 were retrospectively collected.Immunohistochemical staining was used to detect the expression of PD-L1 in the PTC tissues,PD-L1 staining positive cells≥20%was judged as positive expression,<20%was judged as negative expression.The relationship between PD-L1positive expression rate and clinicopathologic characteristics of patients with PTC were analyzed,and the correlation between the presence of HT in PTC tissues and PD-L1 positive expression was studied.Results A total of 138 patients with PTC were included in this study,including 104 patients with PTC alone and 34 PTC patients with coexistent HT.The positive rate of PD-L1 expression in the 138 cases of PTC tissues was 35.5%(49/138),among which was 43.3%(45/104)in the pure PTC tissues,and 11.8%(4/34)in the PTC tissues with HT,the latter was significantly lower than the former(P=0.001).The results of univariate analysis showed that the positive rate of PD-L1 expression was related to the tumor size,the presence or absence of extraglandular invasion and HT in PTC patients(P<0.05),and the results of Spearman correlation analysis showed that the positive rate of PD-L1 expression was positively correlated with tumor size(r_(s)=0.173,P=0.041)and extraglandular invasion(r_(s)=0.197,P=0.021),and negatively correlated with whether TH was merged(r_(s)=–0.284,P=0.001).The multivariate analysis results showed that the positive rate of PD-L1 expression was closely related to whether PTC with coexistent HT[OR=5.720,95%CI(1.879,17.411),P=0.002],and it was not found to be related to tumor size and presence of extraglandular invasion(P>0.05).Conclusions Positive rate of PD-L1 expression has a certain relationship with tumor size and presence or absence of extraglandular invasion,and which in PTC patients with or without HT is significantly different,that is,positive rate of PD-L1 expression in PTC with HT is lower suggests that coexistent HT might be an inhibitory factor in occurrence of PTC,and immune microenvironment-related factors of PTC might be involved in occurrence and development of thyroid cancer.