HLA-G Expression in Human Breast Cancer: Implications for Diagnosis and Prognosis, and Effect on Allocytotoxic Lymphocyte Response After Hormone Treatment In Vitro

Abstract

The aim of this study is to investigate clinical implications of human leukocyte antigen-G (HLA-G) expression in breast cancer. HLA-G expression in 235 primary breast cancer tissues was investigated using immunohistochemistry, and plasma soluble HLA-G (sHLA-G) was measured in 44 breast cancer patients using a specific HLA-G enzyme-linked immunosorbent assay (ELISA). Effects of estradiol/progesterone and their antagonists tamoxifen/RU486 on HLA-G expression in cultured breast cancer MCF-7 cells were determined by real-time polymerase chain reaction (PCR) and the ELISA. Alterations of HLA-G expression by the hormone treatments on subsequent allocytotoxic lymphocyte (allo-CTL) response were also examined. In the study, approximately 66% of neoplasm lesions were identified to have positive HLA-G expression. This expression was significantly correlated with tumor size, nodal status, and clinical disease stage (P = 0.0001, 0.012, and 0.0001, respectively). Patients with positive HLA-G expression had a lower survival rate than those with negative expression (P < 0.028). Plasma sHLA-G levels were significantly higher in breast cancer patients than in healthy controls (P < 0.001), with the area under the receiver-operating characteristic (ROC) curve being 0.95. HLA-G expression in breast cancer MCF-7 cells was enhanced by estradiol/progesterone but reduced by their antagonists. Cytotoxicity studies showed that allo-CTL response in MCF-7 cells was inhibited by prior treatment with estradiol/progesterone, but was amplified by their antagonists. The effects could be restored or further strengthened by the addition of anti-HLA-G antibodies. Our findings suggest that HLA-G may have potential clinical implications in diagnosis, prognosis, and immunotherapy of patients with breast cancer.