title: Scoring of PD-L1 expression intensity on pulmonary adenocarcinomas and the correlations with clinicopathological factors.
abstract: BACKGROUND
  The contribution of programmed cell death ligand-1 (PD-L1) immune checkpoint molecule toward progression of non-small cell lung cancer (NSCLC) has not yet been elucidated, in part, because of lack of a standardised method to evaluate PD-L1 expression. In this study, we developed a novel method for the evaluation of PD-L1 expression on NSCLC cells and examined its correlation with clinicopathological characteristics.
  
  
  METHODS
  After immunohistochemical examination of PD-L1 expression for surgically resected pulmonary adenocarcinomas (n=106), based on the findings that PD-L1 are consistently expressed on alveolar macrophages, PD-L1 staining intensity of tumour cells was classified into four levels relative to PD-L1 staining intensity in alveolar macrophages; PD-L1 expression scores (range, 0-300) were semiquantitatively assessed. An analysis of statistical association between PD-L1 expression score and clinicopathological characteristics was performed.
  
  
  RESULTS
  Almost all of the alveolar macrophages in the specimens were moderately to strongly stained with PD-L1, serving as an internal positive control in the immunohistochemistry of PD-L1. PD-L1 expression score (median, 52.3) was significantly higher in tumours with G2/3 differentiation than in those with G1 (p=0.022) and higher in those with lymphatic invasion than in those without invasion (p=0.032). Postoperative relapse-free survival was significantly shorter in patients with a high PD-L1 expression score than in those with low PD-L1 expression score (p=0.035). Smoking habits, histological subtype, andepidermal growth factor receptormutation status were not associated with PD-L1 expression score.
  
  
  CONCLUSIONS
  Given the heterogeneous distribution of PD-L1 expression in pulmonary adenocarcinoma cells, the scoring of PD-L1 expression on tumour cells relative to that in alveolar macrophages appears to be a valid indicator of PD-L1 status of patients with pulmonary adenocarcinomas, demonstrating a significant correlation with several factors associated with tumour progression.
authors.affiliation: Department of Medical Oncology, Shiga University of Medical Science, Otsu, Japan; Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Department of Medical Oncology, Shiga University of Medical Science, Otsu, Japan; Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Teramoto
authors.affiliation: Department of Clinical Laboratory Medicine , Shiga University of Medical Science , Otsu , Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Department of Surgery , Shiga University of Medical Science , Otsu , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hanaoka
authors.affiliation: Department of Medical Oncology, Shiga University of Medical Science, Otsu, Japan; Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
keywords: Alveolar macrophage; Expression score; Immunohistochemistry; Programmed cell death-ligand 1; Pulmonary adenocarcinoma