PD-L1 (22C3) Expression Correlates with Clinical and Molecular Features of Lung Adenocarcinomas in Cytological Samples

Sarah A. Anderson, Djamel Harbi, Diana Oramas Mogrovejo, Antoinette D. Floyd, Isam Eldin Eltoum, Huma Fatima, Frida Rosenblum, Manuel Lora Gonzalez, Diana Lin, Alexander C. Mackinnon, Gene P. Siegal, Thomas Winokur, Ceren Yalniz, Lei Huo, Shuko Harada, Xiao Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: PD-L1 expression is the most widely used predictive marker for immune checkpoint inhibitor (ICI) therapy in patients with lung adenocarcinoma. However, the current understanding of the association between PD-L1 expression and treatment response is suboptimal. A significant percentage of patients have only a cytological specimen available for clinical management. Therefore, it is relevant to examine the impact of molecular features on PD-L1 expression in cytological samples and how it might correlate with a therapeutic response. Methods: We evaluated patients diagnosed with adenocarcinoma of the lung who had both in-house targeted next-generation sequencing analysis and paired PD-L1 (22C3) immunohistochemical staining performed on the same cell blocks. We explored the association between molecular features and PD-L1 expression. In patients who underwent ICIs therapy, we assessed how a specific gene mutation impacted a therapeutic response. Results: 145 patients with lung adenocarcinoma were included in this study. PD-L1-high expression was found to be more common in pleural fluid than in other sample sites. Regional lymph node samples showed a higher proportion of PD-L1-high expression (29%) compared with lung samples (6%). The predictive value of PD-L1 expression was retained in cytological samples. Mutations in KRAS were also associated with a PD-L1-high expression. However, tumors with TP53 or KRAS mutations showed a lower therapy response rate regardless of the PD-L1 expression. Conclusion: Cytological samples maintain a predictive value for PD-L1 expression in patients with lung adenocarcinoma as regards the benefit of ICI treatment. Specific molecular alterations additionally impact PD-L1 expression and its predictive value.

Original languageEnglish (US)
Pages (from-to)507-518
Number of pages12
JournalActa cytologica
Volume67
Issue number5
DOIs
StatePublished - Oct 1 2023

Bibliographical note

Publisher Copyright:
© 2023 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

Keywords

  • Cell block
  • Lung adenocarcinoma
  • Molecular profiling
  • PD-L1

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