Therapeutic Advances in Medical Oncology (Oct 2020)

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
https://doi.org/10.1177/1758835920965840
Journal volume & issue
Vol. 12

Abstract

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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.