The importance of histological patterns on PD-L1 staining heterogeneity: Should we use pattern-based approach for selecting tumor samples for PD-L1 testing in lung adenocarcinomas?

Turk J Med Sci. 2021 Feb 26;51(1):204-213. doi: 10.3906/sag-2004-61.

Abstract

Background/aim: Programmed death ligand-1 (PD-L1) is a predictive marker for immunotherapeutic agents. However, heterogeneous staining of PD-L1 can cause false-negative results. The aim of this study is to evaluate the importance of histological patterns on PD-L1 staining heterogeneity in lung adenocarcinomas (LAC).

Materials and methods: PD-L1 immunohistochemistry (IHC) stain was performed to two different tissue cores of 128 LAC cases, and cut-off values are given for grouping the cases according to the percentage of staining (1%-10%, 11%-49%, 50%-100%). Staining rates between cores were compared and analyzed by their histological patterns. Also, the relation of the PD-L1 expression with the clinicopathological characteristics of the cases was analyzed.

Results: Overall, PD-L1 expression was observed in 53 of 128 cases (41.4%, 1% cut-off), 23.5% of them were positive at 10% cut-off and 14.1% at 50% cut-off. PD-L1 expression was significantly related to the high grade micropapillary and solid patterns of adenocarcinomas (p:0.01). Staining cut-offs were mostly similar between cores (43/50, 86%) (k:0.843). However, 14% of them were positive only in one core (7 of 50). This false negativity was mostly related to the histological patterns.

Conclusion: Our data reveal the heterogeneous staining of PD-L1 expression, also micropapillary and solid patterns show higher rates of PDL expression. Therewithal, these findings also highlight the importance of taking into consideration of histological patterns, when choosing a paraffin block for the PDL1.

Keywords: PD-L1; immunotherapy; lung adenocarcinoma; lung cancer.

MeSH terms

  • Adenocarcinoma of Lung* / immunology
  • Adenocarcinoma of Lung* / pathology
  • Adenocarcinoma of Lung* / therapy
  • B7-H1 Antigen* / antagonists & inhibitors
  • B7-H1 Antigen* / immunology
  • B7-H1 Antigen* / metabolism
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry / methods*
  • Immunotherapy / methods
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neoplasm Staging
  • Patient Selection
  • Staining and Labeling* / methods
  • Staining and Labeling* / statistics & numerical data

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human