Loss of heterozygosity at 6p21 underling HLA class I downregulation in Chinese primary esophageal squamous cell carcinomas

Abstract

Loss or downregulation of human leukocyte antigen (HLA) class I molecules is a widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic T lymphocytes favoring tumor immune escape. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes, such as the loss of heterozygosity (LOH) at chromosome region 6p21.3. In this study, we used immunohistological techniques with a highly selective panel of anti-HLA monoclonal antibodies to analyze the expression of HLA class I molecules in 84 formalin-fixed, paraffin-embedded section and 49 frozen-fresh tissues of primary esophageal squamous cell carcinomas (pESCC) from Chinese patients. To elucidate the underlying mechanism of HLA class I loss or downregulation, we also analyzed LOH of previously selected microsatellite markers located in chromosomes 6 and 15 by polymerase chain reaction. DNA was obtained from frozen-fresh tumor tissues and surrounding stroma to define the LOH associated with chromosomes 6p21 and 15q21. Our results showed that HLA-A, HLA-B/C, HLA class I heavy chain, beta2-microglobuline, and HLA class I complex were lost or downregulated in pESCC (P<0.0001), and were moderately associated with the microsatellite alterations in HLA class I gene regions, correlated with patients' age, tumor's location, and stage, and indicated that LOH at 6p21.3 is a frequent mechanism that leads to HLA class I abnormalities in pESCC.