HLA-G expression in human breast cancer: implications for diagnosis and prognosis, and effect on allocytotoxic lymphocyte response after hormone treatment in vitro

Abstract

Objective: The aim of this study is to investigate clinical implications of human leukocyte antigen-G (HLA-G) expression in breast cancer.

Methods: 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.

Results: 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.

Conclusion: Our findings suggest that HLA-G may have potential clinical implications in diagnosis, prognosis, and immunotherapy of patients with breast cancer.