Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer

• Published in: Journal of pathology and translational medicine Vol. 53; no. 2; pp. 75 - 85
• Main Authors: Park, Hong Sik, Cho, Uiju, Im, So Young, Yoo, Chang Young, Jung, Ji Han, Suh, Young Jin, Choi, Hyun Joo
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Pathologists, Korean Society for Cytopathology 01.03.2019; The Korean Society of Pathologists and the Korean Society for Cytopathology; Korean Society of Pathologists & the Korean Society for Cytopathology; 대한병리학회
• Subjects: Antigens; Archives & records; Breast cancer; Breast neoplasms; Chemotherapy; HLA antigens; Hospitals; Lymphocytes; Lymphocytes, tumor-infiltrating; Major histocompatibility complex; Medical prognosis; Medical records; Metastasis; Original; Patients; Survival analysis; T-lymphocytes, regulatory; Tumors; 병리학; breast cancer; tumor-infiltrating lymphocytes; major histocompatibility complex; human leukocyte antigen; regulatory T-lymphocytes
• ISSN: 2383-7837; 2383-7845
• DOI: 10.4132/jptm.2018.10.11

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.