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Research ArticleClinical Studies

Molecular Characteristics of Lymphocyte-predominant Triple-negative Breast Cancer

RITSUKO SASAKI, YOSHIYA HORIMOTO, YUKA YANAI, AIKO KURISAKI-ARAKAWA, ATSUSHI ARAKAWA, KATSUYA NAKAI, MITSUE SAITO and TSUYOSHI SAITO
Anticancer Research April 2021, 41 (4) 2133-2140; DOI: https://doi.org/10.21873/anticanres.14985
RITSUKO SASAKI
1Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan;
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YOSHIYA HORIMOTO
1Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan;
2Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
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  • For correspondence: horimoto@juntendo.ac.jp
YUKA YANAI
2Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
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AIKO KURISAKI-ARAKAWA
2Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
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ATSUSHI ARAKAWA
2Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
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KATSUYA NAKAI
1Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan;
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MITSUE SAITO
1Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan;
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TSUYOSHI SAITO
2Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
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Abstract

Background/Aim: Tumor-infiltrating lymphocytes (TILs) are considered a prognostic marker for triple-negative breast cancer (TNBC). Immune checkpoint inhibitor (ICI)-based treatments are more effective for tumors with PD-L1-positive TILs, suggesting crucial roles of TILs in the local tumor immunity. However, factors attracting TILs are still largely unknown. Focusing on tumor antigenicity, we examined TNBC samples to identify the characteristics of TIL-high tumors. Patients and Methods: Nine treatment-naïve TNBCs (TIL-high: five, TIL-low: four) were subjected to next-generation sequencing (NGS). Loss of heterozygosity (LOH) of PTEN was also analyzed. Results: A variety of copy number variations were observed, and no genes differed significantly between TIL-high and -low groups. However, PTEN loss was more frequently observed in the TIL-high group: 60% compared to 25% in TIL-low tumors. NGS correlated well with LOH analysis in identifying PTEN loss. All three tumors with PTEN loss in the TIL-high group showed high PD-L1. All nine samples were microsatellite-stable. Conclusion: Frequent PTEN loss and high expression of PD-L1 in TIL-high TNBC suggest that PTEN mutation may be a biomarker for ICIs.

Key Words:
  • Tumor-infiltrating lymphocytes
  • triple-negative breast cancer
  • PTEN
  • PD-L1
  • immune checkpoint inhibitor
  • microsatellite instability
  • Received February 12, 2021.
  • Revision received February 22, 2021.
  • Accepted February 23, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Molecular Characteristics of Lymphocyte-predominant Triple-negative Breast Cancer
RITSUKO SASAKI, YOSHIYA HORIMOTO, YUKA YANAI, AIKO KURISAKI-ARAKAWA, ATSUSHI ARAKAWA, KATSUYA NAKAI, MITSUE SAITO, TSUYOSHI SAITO
Anticancer Research Apr 2021, 41 (4) 2133-2140; DOI: 10.21873/anticanres.14985

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Molecular Characteristics of Lymphocyte-predominant Triple-negative Breast Cancer
RITSUKO SASAKI, YOSHIYA HORIMOTO, YUKA YANAI, AIKO KURISAKI-ARAKAWA, ATSUSHI ARAKAWA, KATSUYA NAKAI, MITSUE SAITO, TSUYOSHI SAITO
Anticancer Research Apr 2021, 41 (4) 2133-2140; DOI: 10.21873/anticanres.14985
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Keywords

  • tumor-infiltrating lymphocytes
  • triple-negative breast cancer
  • PTEN
  • PD-L1
  • immune checkpoint inhibitor
  • microsatellite instability
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