甲状腺乳头状癌中PD-L1蛋白表达与BRAF V600E基因突变的相关性

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摘要目的：探讨甲状腺乳头状癌（PTC）中PD-L1蛋白表达与BRAF V600E基因突变的相关性。方法：应用免疫组织化学Envision两步法检测74例PTC及癌旁正常甲状腺组织的PD-L1蛋白表达，Q-PCR法检测PTC组织中BRAF V600E基因突变情况，分析PD-L1蛋白表达与PTC各临床病理特征及BRAF V600E基因突变的相关性。结果：PD-L1阳性表达于48.6%（36/74）的PTC组织中，高于癌旁对照组（P＜0.01）。PD-L1蛋白在PTC中的表达与年龄、肿瘤大小、淋巴细胞性甲状腺炎（CLT）背景、肿瘤浸润淋巴细胞（TILs）以及临床分期有关（P＜0.05）。BRAF V600E基因突变的阳性率为79.7%（59/74）。BRAF V600E基因突变与PTC的组织学分型有关（P＜0.01）。PD-L1蛋白表达与BRAF V600E基因突变之间无明显相关性（Kappa=-0.091，P＞0.05）。多因素logistic回归分析显示CLT背景是影响PD-L1蛋白表达的独立因素（OR=18.675，95%CI：3.074～113.453，P＜0.01）。结论：PD-L1蛋白在PTC组织中有过量表达，其阳性表达与PTC的临床病理特征有关，而与BRAF V600E基因突变无关。

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关键词 ：甲状腺乳头状癌, PD-L1, BRAF V600E, 基因突变

Abstract：Objective: To investigate the correlation between PD-L1 protein expression and BRAF V600E gene mutation in papillary thyroid carcinoma (PTC). Methods: 74 cases of PTC and normal thyroid tissue specimens were used to detect PD-L1 protein expression by immunohistochemical EnVision two step method. Gene mutation of BRAF V600E was detected by Q-PCR. And the correlation between PD-L1 protein expression and the clinicopathological parameters of PTC including BRAF V600E gene mutation was evaluated. Results: The positive rate of PD-L1 protein expression was 48.6% (36/74) in PTC tissues, significantly higher than that in control group (P<0.01). The expression of PD-L1 protein was correlated with age, tumor size, chronic lymphocytic thyroiditis (CLT) background, tumor-infiltrating lymphocytes (TILs) and clinical stage (P<0.05). The positive rate of BRAF V600E gene mutation was 79.7% (59/74) in PTC tissues. The gene mutation of BRAF V600E was correlated with histological classification of PTC (P<0.01). Consistency analysis showed that there was no relationship between PD-L1 protein expression and BRAF V600E gene mutation (Kappa=-0.091, P>0.05). Among these parameters, background CLT was independent factor affecting PD-L1 protein expression (OR=18.675, 95%CI: 3.074~113.453, P<0.01). Conclusion: PD-L1 protein is over-expressed in PTC tissues. The expression of PD-L1 protein is correlated with clinicopathologic features of PTC, but there is no relationship between PD-L1 protein expression and BRAF V600E gene mutation in PTC.

Key words： papillary thyroid carcinoma PD-L1 BRAF V600E gene mutation

收稿日期: 2018-04-05

基金资助:浙江省自然科学基金资助项目（LY14H160036）；台州市科技计划项目（1701KY56）。

通讯作者: 梁勇，主任医师，教授，硕士生导师，Email：liangytu@aliyun.com。

作者简介: 罗华荣（1980-），男，浙江台州人，副主任医师，在职硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I10/718

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