Loss of heterozygosity at 6p21 underlying [corrected] HLA class I downregulation in Chinese primary esophageal squamous cell carcinomas.
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.
Yang
Y
Y
Key Laboratory of Developmental Genes and Human Disease of Education Ministry, Department of Genetics and Developmental Biology, Southeast University Medical School, Nanjing, Jiangsu, China.
Zhang
J
J
Miao
F
F
Wei
J
J
Shen
C
C
Shen
Y
Y
Xie
W
W
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002681:China; D002884:Chromosomes, Human, Pair 15; D002896:Chromosomes, Human, Pair 6; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity / Q000276:immunology; D018895:Microsatellite Repeats; D008875:Middle Aged; D016612:Paraffin Embedding
D015395:Histocompatibility Antigens Class I