Abstract

Background/aimProgrammed 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. ResultsOverall, 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.ConclusionOur 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.

Highlights

  • Lung cancer is the leading cause of cancer related mortality worldwide and one of the most highly mutated ones among solid tumors

  • Programmed death ligand-1 (PD-L1) expression was significantly related to the high grade micropapillary and solid patterns of adenocarcinomas (p:0.01)

  • Our data reveal the heterogeneous staining of PD-L1 expression, micropapillary and solid patterns show higher rates of PDL expression

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Summary

Introduction

Lung cancer is the leading cause of cancer related mortality worldwide and one of the most highly mutated ones among solid tumors. Many lung cancer patients have a high mutational burden [1]. Nonsmall cell lung cancer (NSCLC) accounts for the majority of lung cancer cases (80%-85%) [2,3]. Most patients have locally advanced or metastatic disease on initial presentation. The treatment options for advanced or metastatic disease were typically confined to chemotherapy or radiation therapy, but the advent of targeted therapies as EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) inhibitors have led to improved outcome in some patients who harbor driver oncogenes, especially in lung adenocarcinomas [4,5]. Immunotherapy represented a new and highly promising therapeutic option for metastatic

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