Breast Cancer: Targets and Therapy (Jan 2024)
The Programmed Cell Death Ligand 1 and Lipocalin 2 Expressions in Primary Breast Cancer and Their Associations with Molecular Subtypes and Prognostic Factors
Abstract
Suheyla Ekemen,1,2 Ebru Bilir,3 Hagar Elsayed Akram Soultan,3 Sadia Zafar,3 Figen Demir,4 Babek Tabandeh,5 Sadik Toprak,6 Ozlem Yapicier,7 Cevayir Coban2,8,9 1Vocational School of Health Services, Acibadem University, Istanbul, Turkey; 2Division of Malaria Immunology, Department of Microbiology and Immunology, Institute of Medical Science (IMSUT), the University of Tokyo, Tokyo, Japan; 3Residency Program, Bahcesehir University School of Medicine, Istanbul, Turkey; 4Department of Public Health, Acibadem University School of Medicine, Istanbul, Turkey; 5Department of General Surgery, Bahcesehir University School of Medicine, Istanbul, Turkey; 6Department of Forensic Medicine, Istanbul University School of Medicine, Istanbul, Turkey; 7Department of Pathology, Bahcesehir University School of Medicine, Istanbul, Turkey; 8Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan; 9International Vaccine Design Center, Institute of Medical Science (IMSUT), the University of Tokyo, Tokyo, JapanCorrespondence: Suheyla Ekemen, Division of Malaria Immunology, Department of Microbiology and Immunology the Institute of Medical Science (IMSUT), the University of Tokyo Building 1, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, Email [email protected]; [email protected]: Breast cancers exhibit molecular heterogeneity, leading to diverse clinical outcomes and therapeutic responses. Immune checkpoint inhibitors targeting PD-L1 have shown promise in various malignancies, including breast cancer. Lipocalin 2 (LCN2) has also been associated with tumor aggressiveness and prognostic potential in breast cancers. However, the expression of PD-L1 and LCN2 in breast cancer subtypes and their prognostic implications remains poorly investigated.Methods: A retrospective analysis of 89 primary breast cancer cases was conducted to assess PD-L1 and LCN2 expressions using immunohistochemistry. Cases were classified into four different molecular subtypes based on ER, PR, HER2, and Ki-67 status. Associations between PD-L1 and LCN2 expressions and various prognostic factors were examined.Results: Although low expression of LCN2 (Allred score of < 3) was observed even in normal breast tissue, LCN2 expression with increasing Allred score (≥ 3) positively correlated with the histological grade, high Ki-67 proliferation index, and ER/PR negativity. Significant elevations of LCN2 and PD-L1 expressions were observed in triple-negative and HER2-positive breast cancers.Conclusion: The results of the study highlight the association of LCN2 with known prognostic factors and molecular subtypes. To identify potential immunotherapy recipients, it would be useful to evaluate LCN2 as well as PD-L1 immune targets in different subgroups of breast cancer patients. Further studies with larger patient numbers are warranted to validate these observations and establish standardized scoring criteria for LCN2 expression assessment.Keywords: breast cancer, immunotherapy, PD-L1, LCN2, triple-negative breast cancer, TNBC
