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

Caichen Li; Jun Liu; Zhanhong Xie; Feng Zhu; Bo Cheng; Hengrui Liang; Jianfu Li; Shan Xiong; Zisheng Chen; Zhichao Liu; Yi Zhao; Limin Ou; Ran Zhong; Wei Wang; Jun Huang; Jinyun Sun; Chunya Zhang; Landong Weng; Jianxing He; Wenhua Liang; Zhenkui Pan

doi:10.1177/1758835920965840

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

Ther Adv Med Oncol. 2020 Oct 17:12:1758835920965840. doi: 10.1177/1758835920965840. eCollection 2020.

Authors

Caichen Li¹, Jun Liu¹, Zhanhong Xie², Feng Zhu¹, Bo Cheng¹, Hengrui Liang¹, Jianfu Li¹, Shan Xiong¹, Zisheng Chen¹, Zhichao Liu³, Yi Zhao¹, Limin Ou¹, Ran Zhong¹, Wei Wang¹, Jun Huang¹, Jinyun Sun⁴, Chunya Zhang⁴, Landong Weng⁴, Jianxing He¹, Wenhua Liang⁵, Zhenkui Pan⁶

Affiliations

¹ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China.
² Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, China.
³ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁴ Medical Affairs, LinkDoc Technology Co., Ltd., Beijing, China.
⁵ 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.
⁶ 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.

Keywords: SP142; driver mutations; immunohistochemistry; non-small cell lung cancer; programmed cell death ligand 1 (PD-L1); real world study.