title: Methylation of the promoter of human leukocyte antigen class I in human esophageal squamous cell carcinoma and its histopathological characteristics.
abstract: OBJECTIVE
  The downregulation of human leukocyte antigen class I (HLA-I) has been proposed to contribute to the immune evasion of cancer cells in some cancers. Meanwhile, transcriptional silencing by means of promoter methylation is now believed to be an important mechanism of carcinogenesis. The aim of this study was (1) to examine the expression of HLA-I antigen and the antigen-processing machinery components in patients with esophageal squamous cell carcinoma lesions and (2) to detect the methylation pattern of the HLA-I gene in patients with esophageal squamous cell carcinoma and assess its association with histopathological characteristics.
  
  
  METHODS
  A total of 87 formalin-fixed and paraffin-embedded esophageal squamous cell carcinoma lesions were collected. HLA-I and antigen-processing machinery component expression was investigated by means of immunohistochemistry with anti-HLA-I monoclonal antibody, and methylation changes in the promoter region of HLA-1 genes were determined by using methylation-specific polymerase chain reaction.
  
  
  RESULTS
  HLA-I, transporter associated with antigen processing 1, and low molecular weight protein were lost or downregulated in 67%, 29.8%, and 47.0% of the esophageal squamous cell carcinoma lesions, respectively. The positive rates of gene promoter hypermethylation of HLA-I was 70.1% (61/87) in tumor tissues compared with 3.6% in normal tissue (P < .01). Also, the higher methylation rates and the HLA-I expression were significantly associated with tumor grade, including lymph node metastasis (P < .05).
  
  
  CONCLUSIONS
  HLA-I promoter hypermethylation was associated with loss of HLA-I antigen, which frequently occurred in primary tumors, especially in metastatic lymph node lesions, and was associated with patients' prognoses.
authors.affiliation: Thoracic Surgery, Second Hospital of Shandong University, Jinan, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Qifeng
authors.forename: Cong
authors.initials: C
authors.lastname: Bo
authors.forename: Jiang
authors.initials: J
authors.lastname: Xingtao
authors.forename: Peng
authors.initials: P
authors.lastname: Chuanliang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Xiaogang
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D002681:China; D018899:CpG Islands; D003546:Cysteine Endopeptidases / Q000032:analysis; D019175:DNA Methylation; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D005260:Female; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C477327:transporter associated with antigen processing (TAP); C071313:LMP-2 protein; D003546:Cysteine Endopeptidases