Methylation of the promoter of human leukocyte antigen class I in human esophageal squamous cell carcinoma and its histopathological characteristics

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. (J Thorac Cardiovasc Surg 2011;141:808-14)