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

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.

Keywords: Adenocarcinoma; Cancer immunotherapy; Lung cancer; PD-L1; p53.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • Disease-Free Survival
  • Female
  • Genes, erbB-1 / genetics
  • Genes, p53 / immunology*
  • Humans
  • Immunotherapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasm Staging
  • Prognosis
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Retrospective Studies
  • Smoking / epidemiology

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)