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程序性细胞死亡配体-1在肺腺癌中的表达的临床病理及预后意义及其与p53状态的关系

Clinicopathological and prognostic significance of programmed cell death ligand-1 expression in lung adenocarcinoma and its relationship with p53 status.

作者信息

Cha Yoon Jin, Kim Hye Ryun, Lee Chang Young, Cho Byoung Chul, Shim Hyo Sup

机构信息

Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Department of Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

Lung Cancer. 2016 Jul;97:73-80. doi: 10.1016/j.lungcan.2016.05.001. Epub 2016 May 3.

Abstract

INTRODUCTION

PD-L1 expression is a predictive biomarker for response to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors and can be evaluated by immunohistochemistry. Results of the clinicopathologic characteristics of PD-L1-positive lung adenocarcinoma have been inconsistent in previous studies, and there are no reports on the relationship between PD-L1 expression and p53 status in lung adenocarcinoma.

METHODS

We examined PD-L1 and p53 expression in a total of 323 surgically resected lung adenocarcinoma cases using anti-PD-L1 (clone SP142) and anti-p53 (clone DO-7) antibodies, and analyzed the clinicopathologic characteristics of PD-L1-positive cases and their relationship with p53 status.

RESULTS

PD-L1 expression in tumor cells was positive in 60 of 323 cases (18.6%). Higher PD-L1 expression (≥50%) was more prevalent in former or current smokers (p=0.026) and was associated with more pack-years (p=0.016). PD-L1-positive tumors were significantly associated with solid predominant type (p<0.001), p53 aberrant expression (p<0.001), and PD-L1 expression in tumor-infiltrating immune cells (p<0.001). Patients with stage I to III tumors harboring PD-L1-positive tumor cells showed poor recurrence-free survival (p<0.001) and overall survival (p<0.001) on univariate analysis.

CONCLUSIONS

PD-L1 expression in tumor cells, solid predominant histology, p53 aberrant expression, and PD-L1 expression in tumor-infiltrating immune cells are closely related. These variables should be considered when analyzing the clinical outcomes of patients with lung adenocarcinomas treated with anti-PD1/PD-L1 immune checkpoint inhibitors.

摘要

引言

程序性死亡配体1(PD-L1)表达是预测抗程序性细胞死亡蛋白1(PD-1)/程序性死亡配体1(PD-L1)免疫检查点抑制剂疗效的生物标志物,可通过免疫组织化学进行评估。既往研究中,PD-L1阳性肺腺癌的临床病理特征结果并不一致,且尚无关于肺腺癌中PD-L1表达与p53状态之间关系的报道。

方法

我们使用抗PD-L1(克隆号SP142)和抗p53(克隆号DO-7)抗体,检测了323例手术切除的肺腺癌病例中PD-L1和p53的表达,并分析了PD-L1阳性病例的临床病理特征及其与p53状态的关系。

结果

323例病例中有60例(18.6%)肿瘤细胞中的PD-L1表达呈阳性。较高的PD-L1表达(≥50%)在既往或当前吸烟者中更为普遍(p=0.026),且与更多的吸烟包年数相关(p=0.016)。PD-L1阳性肿瘤与实性为主型显著相关(p<0.001)、p53异常表达(p<0.001)以及肿瘤浸润免疫细胞中的PD-L1表达相关(p<0.001)。单因素分析显示,I至III期肿瘤细胞PD-L1阳性的患者无复发生存期(p<0.001)和总生存期较差(p<0.001)。

结论

肿瘤细胞中的PD-L1表达、实性为主的组织学类型、p53异常表达以及肿瘤浸润免疫细胞中的PD-L1表达密切相关。在分析接受抗PD1/PD-L1免疫检查点抑制剂治疗的肺腺癌患者的临床结局时,应考虑这些变量。

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