title: 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.
  
  
  CONCLUSIONS
  Our findings suggest that HLA-G may have potential clinical implications in diagnosis, prognosis, and immunotherapy of patients with breast cancer.
authors.affiliation: Core Laboratory, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Dong
authors.forename: Shang-mian
authors.initials: SM
authors.lastname: Yie
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Mei
authors.initials: M
authors.lastname: Cao
authors.forename: Shang-rong
authors.initials: SR
authors.lastname: Ye
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D009367:Neoplasm Staging; D011374:Progesterone / Q000494:pharmacology; D011379:Prognosis; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D006727:Hormone Antagonists; D006728:Hormones; D013629:Tamoxifen; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol