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JPTM > Ahead-of Print

doi: https://doi.org/10.4132/jptm.2018.10.11    [Epub ahead of print]
Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer
Hong Sik Park1, Uiju Cho1, So Young Im1, Chang Young Yoo1, Ji Han Jung1, Young Jin Suh2, Hyun Joo Choi1
1Department of Hospital Pathology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
Corresponding Author: Hyun Joo Choi ,Tel: +82-31-249-7592, Fax: +82-31-244-6786, Email: chj0103@catholic.ac.kr
Received: August 9, 2018;  Revised: September 21, 2018  Accepted: October 11, 2018.  Published online: November 14, 2018.

Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.
We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.
Total loss of HLA-I expression was found in 84 (18.1%) breast cancer samples. Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = 0.029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II-IV) (p = 0.031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I-positive tumors than in HLA-I-negative tumors (median 6.3 cells/high power field vs. 2.1 cells/high power field, p < 0.001). However, Tregs were not an independent prognostic factor in our cohort.
Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.
Key Words: breast cancer, human leukocyte antigen, major histocompatibility complex, tumor-infiltrating lymphocytes, regulatory T-lymphocytes