PD-L1 expression with respect to driver mutations in non-small cell lung cancer in an Asian population: a large study of 1370 cases in China

Author:

Li Caichen12,Liu Jun12,Xie Zhanhong34,Zhu Feng12,Cheng Bo12,Liang Hengrui12,Li Jianfu12,Xiong Shan12,Chen Zisheng12,Liu Zhichao5,Zhao Yi12,Ou Limin12,Zhong Ran12,Wang Wei12,Huang Jun12,Sun Jinyun6,Zhang Chunya6,Weng Landong6,He Jianxing12,Liang Wenhua7,Pan Zhenkui8ORCID

Affiliation:

1. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China

2. State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou, China

3. Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, China

4. State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, China

5. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

6. Medical Affairs, LinkDoc Technology Co., Ltd., Beijing, China

7. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, No. 151, Yanjiang Road, Guangzhou, Guangdong Province, China

8. Department of Oncology, Qingdao Municipal Hospital, No. 1 Jiaozhou Road, Qingdao, ShanDong Province, China

Abstract

Background: Programmed cell death ligand 1 (PD-L1) expression with respect to genetic alternations has not been well established in non-small cell lung cancer (NSCLC), especially in the Asian population. Methods: We reviewed 1370 NSCLC patients from a prospectively maintained database. Immunohistochemistry was performed on tumor cells and tumor-infiltrating lymphocytes (TILs) using the VENTANA (SP142) anti-PD-L1 antibody. The tumor proportion score (TPS) cutoff values were set at ⩾1% and ⩾50%, and the immune proportion score (IPS) cutoff values were set at ⩾1% and ⩾10%. Results: In tumor cells, PD-L1 positivity was observed in 405 (29.6%), 122 (8.9%), and 27 (2.0%) patients with TPS cutoff values at ⩾1% and ⩾50%. Contrastingly, TILs of 1154 (84.2%) and 346 (25.3%) patients stained positive at IPS cutoff values of ⩾1% and ⩾50%, respectively. PD-L1 expression was more common in patients who were mutation-negative irrespective of the TPS cutoff values and tumor size. PD-L1 expression in tumor cells was less frequent in patients harboring EGFR mutations (18.8% TPS ⩾ 1% and 4.6% TPS ⩾ 50%). Conversely, PD-L1 expression was high in the presence of KRAS mutations (47.3% TPS ⩾ 1% and 22.5% TPS ⩾ 50%). Overall, KRAS, BRAF, PICK3A, MET mutations and ROS1 and RET translocations were more frequent, while EGFR and HER2 mutations and ALK translocations were less frequent compared with the overall PD-L1 expression levels. Although the difference between TILs among the PD-L1-positive cases was comparatively small, PD-L1 positivity was less prevalent in EGFR-mutated tumors and more common in those with KRAS mutations, ROS1 translocations, BRAF mutations, or MET mutations. Conclusion: Our study showed the heterogeneity in PD-L1 expression with respect to nine major oncogenic drivers in China. Future studies are warranted to further clarify the association between PD-L1 expression and driver mutations in NSCLC.

Funder

China National Science Foundation

Guangzhou Scientific Research Project

Publisher

SAGE Publications

Subject

Oncology

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