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Prognostic and Clinicopathologic Associations of LAG-3 Expression in Triple-negative Breast Cancer

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  1. Ovarian Clear Cell Carcinoma: From Morphology to Molecular Biology

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  2. Expression Patterns of Biomarkers in Primary Tumors and Corresponding Metastases in Breast Cancer

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  1. Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer

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  2. Substantial Lymphovascular Space Invasion Is an Adverse Prognostic Factor in High-risk Endometrial Cancer

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  3. Identification of Stably Expressed Reference microRNAs in Epithelial Ovarian Cancer

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  4. CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer-A Multicenter Analysis

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  5. MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma

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The immune checkpoint molecule lymphocyte activation gene 3 (LAG-3) is currently being investigated as a possible target for immunotherapy in triple-negative breast cancer (TNBC), frequently as an addition to treatment with programmed cell death protein 1/programmed death ligand 1 (PD-L1) inhibition. However, expression of LAG-3, the frequency of coexpression with PD-L1, and the prognostic significance of this marker have not been studied extensively in TNBC. For this study, tissue microarrays (TMAs) were constructed from surgical specimens of 514 patients with TNBC. TMAs were stained immunohistochemically for LAG-3 and PD-L1 expression. Tumor-infiltrating lymphocytes (TILs) were evaluated on full glass slides. LAG-3 expression was significantly associated with improved overall survival and relapse-free survival. When adjusted for clinicopathologic factors, each increment of 10 LAG-3-positive intratumoral lymphocytes per TMA core was associated with improved overall survival (hazard ratio=0.93, 95% confidence interval: 0.89-0.97, P=0.002), and recurrence-free survival (hazard ratio=0.91, 95% confidence interval: 0.85-0.97, P=0.002). PD-L1 expression on immune cells and PD-L1 expression evaluated with the combined positive score and TILs were also associated with improved survival in both univariate and multivariate analyses. PD-L1 expression on tumor cells was only associated with improved survival in univariate analysis. LAG-3 expression was associated with both TILs and PD-L1 expression. Coexpression of LAG-3 and PD-L1 did not confer additional survival benefits. In conclusion, LAG-3 expression is associated with improved survival in TNBC. LAG-3 is often coexpressed with PD-L1, confirming that TNBC is likely a suitable candidate for cotreatment with LAG-3 and programmed cell death protein 1/PD-L1 inhibitors. However, coexpression does not confer additional survival benefits.

Original languageEnglish
JournalApplied Immunohistochemistry and Molecular Morphology
Volume30
Issue number1
Pages (from-to)62-71
Number of pages10
ISSN1541-2016
DOIs
Publication statusPublished - 2022

Bibliographical note

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

    Research areas

  • biomarker, immunotherapy, LAG-3, PD-L1, triple-negative breast cancer

ID: 69768121