PMID- 18721270 OWN - NLM STAT- MEDLINE DCOM- 20081020 LR - 20080825 IS - 0001-2815 (Print) IS - 0001-2815 (Linking) VI - 72 IP - 2 DP - 2008 Aug TI - Loss of heterozygosity at 6p21 underlying [corrected] HLA class I downregulation in Chinese primary esophageal squamous cell carcinomas. PG - 105-14 LID - 10.1111/j.1399-0039.2008.01078.x [doi] AB - 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. FAU - Yang, Y AU - Yang Y AD - Key Laboratory of Developmental Genes and Human Disease of Education Ministry, Department of Genetics and Developmental Biology, Southeast University Medical School, Nanjing, Jiangsu, China. FAU - Zhang, J AU - Zhang J FAU - Miao, F AU - Miao F FAU - Wei, J AU - Wei J FAU - Shen, C AU - Shen C FAU - Shen, Y AU - Shen Y FAU - Xie, W AU - Xie W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Tissue Antigens JT - Tissue antigens JID - 0331072 RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Adult MH - Aged MH - Carcinoma, Squamous Cell/*genetics/immunology/pathology MH - Case-Control Studies MH - China MH - Chromosomes, Human, Pair 15 MH - *Chromosomes, Human, Pair 6 MH - Down-Regulation/genetics/immunology MH - Esophageal Neoplasms/*genetics/immunology/pathology MH - *Genes, MHC Class I MH - Histocompatibility Antigens Class I/immunology/metabolism MH - Humans MH - *Loss of Heterozygosity/immunology MH - Microsatellite Repeats MH - Middle Aged MH - Paraffin Embedding EDAT- 2008/08/30 09:00 MHDA- 2008/10/22 09:00 CRDT- 2008/08/30 09:00 PHST- 2008/08/30 09:00 [pubmed] PHST- 2008/10/22 09:00 [medline] PHST- 2008/08/30 09:00 [entrez] AID - TAN1078 [pii] AID - 10.1111/j.1399-0039.2008.01078.x [doi] PST - ppublish SO - Tissue Antigens. 2008 Aug;72(2):105-14. doi: 10.1111/j.1399-0039.2008.01078.x.