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程序性死亡配体1(PD-L1)在东亚非小细胞肺癌中的独特表达分布。

Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer.

作者信息

Pan Yunjian, Zheng Difan, Li Yuan, Cai Xu, Zheng Zongli, Jin Yan, Hu Haichuan, Cheng Chao, Shen Lei, Wang Jian, Ji Hongbin, Sun Yihua, Zhou Xiaoyan, Chen Haiquan

机构信息

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

出版信息

J Thorac Dis. 2017 Aug;9(8):2579-2586. doi: 10.21037/jtd.2017.08.61.

Abstract

BACKGROUND

To determine the proportion and clinical features of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer (NSCLC).

METHODS

PD-L1 expression was assessed by immunohistochemistry (IHC) and tumor proportion score (TPS) with the use of PD-L1 IHC 22C3 antibody (Dako North America) in 108 surgically resected lung squamous cell carcinomas (SCC) and 221 lung adenocarcinomas (LUADs), and was correlated with clinical variables, histologic subtypes, and common driver mutations.

RESULTS

Positive PD-L1 expression was found in 37 lung SCC (37/108, 34.3%), including 15 cases with TPS ≥50% (15/108, 13.9%) and 22 cases with TPS <50% (22/108, 20.4%). In adenocarcinoma cohort, 9 cases were found PD-L1 expression positive (9/221, 4.1%), including 1 case with TPS ≥50% (1/221, 0.5%) and 8 cases with TPS <50% (8/221, 3.9%). Totally, high PD-L1 expression (TPS ≥50%) was significantly associated with male sex (P=0.026), current/ever smoking history (P=0.008) and SCC subtype (P<0.001). Positive PD-L1 expression (including TPS ≥50% and TPS <50%) in LUAD cohort was significantly associated with male sex (P=0.046), current/ever smoking history (P=0.002), mutation pan-negative status (P=0.038), solid-predominant subtype (P<0.001), large tumor size (P=0.027) and lymph node metastasis (P=0.019). No significant difference was found between PD-L1 high expression group (TPS ≥50%) and low/negative expression group in SCC cohort.

CONCLUSIONS

This study revealed the unique distribution of PD-L1 expression in East Asian NSCLCs, which is largely different from Western populations. Since the high response rate of pembrolizumab in the treatment of lung cancer patients with PD-L1 TPS ≥50%, this result indicates that prospective PD-L1 expression testing in specific East Asian patients could facilitate decision making for immunotherapy.

摘要

背景

确定东亚非小细胞肺癌(NSCLC)中程序性死亡配体1(PD-L1)表达的比例及临床特征。

方法

采用免疫组织化学(IHC)和肿瘤比例评分(TPS),使用PD-L1 IHC 22C3抗体(达科北美公司)对108例手术切除的肺鳞状细胞癌(SCC)和221例肺腺癌(LUAD)进行PD-L1表达评估,并将其与临床变量、组织学亚型和常见驱动基因突变相关联。

结果

在37例肺SCC中发现PD-L1表达阳性(37/108,34.3%),其中15例TPS≥50%(15/108,13.9%),22例TPS<50%(22/108,20.4%)。在腺癌队列中,9例PD-L1表达阳性(9/221,4.1%),其中1例TPS≥50%(1/221,0.5%),8例TPS<50%(8/221,3.9%)。总体而言,高PD-L1表达(TPS≥50%)与男性(P=0.026)、当前/既往吸烟史(P=0.008)和SCC亚型(P<0.001)显著相关。LUAD队列中PD-L1表达阳性(包括TPS≥50%和TPS<50%)与男性(P=0.046)、当前/既往吸烟史(P=0.002)、全阴性突变状态(P=0.038)、实性为主亚型(P<0.001)、肿瘤体积大(P=0.027)和淋巴结转移(P=0.019)显著相关。SCC队列中PD-L1高表达组(TPS≥50%)与低/阴性表达组之间未发现显著差异。

结论

本研究揭示了东亚NSCLC中PD-L1表达的独特分布,这与西方人群有很大不同。鉴于帕博利珠单抗治疗PD-L1 TPS≥50%的肺癌患者的高缓解率,该结果表明对特定东亚患者进行前瞻性PD-L1表达检测有助于免疫治疗的决策。

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