Multiple mechanisms generate HLA class I altered phenotypes in laryngeal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21.
Major histocompatibility complex (MHC) class I loss or downregulation in cancer cells is a major immune escape route used by a large variety of human tumors to evade anti-tumor immune responses mediated by cytotoxic T lymphocytes. Multiple mechanisms are responsible for such HLA class I alterations. However, the precise frequency of these molecular defects has not been clearly determined in tumors derived from specific tissues. To analyze such defects we aim to define the major HLA class I-altered phenotypes in different tumor types. In this paper we report on HLA class I expression in 70 laryngeal carcinomas. We used immunohistological techniques with a highly selective panel of anti-HLA monoclonal antibodies (mAb), and polymerase chain reaction (PCR) microsatellite amplification of previously selected microsatellite markers (STR) located in chromosome 6 and 15. DNA was obtained from microdissected tumor tissues and surrounding stroma to define the loss of heterozygosity (LOH) associated with chromosome 6p21. Our results showed that LOH in chromosome 6 produced HLA haplotype loss (phenotype II) in 36% of the tumors. In addition, HLA class I total loss (phenotype I) was found in 11%; HLA A or B locus downregulation (phenotype III) was detected in 20%; and HLA class I allelic loss (phenotype IV) in 10% of all cases. We sometimes observed two or more associated mechanisms in the same HLA-altered phenotype, such as LOH and HLA total loss in phenotype I. In only 23% of tumors it was not possible to identify any HLA class I alteration. We conclude that the combination of immunohistological techniques and molecular analysis of tumor DNA obtained from microdissected tumor tissues provides a means for the first time of determining the actual frequency of the major HLA class I-altered phenotypes in laryngeal carcinomas.
Departamento de Análisis Clínicos, Hospital UniversitarioVirgen de las Nieves, Universidad de Granada, Avd. Fuerzas Armadas 2, 18014 Granada, Spain.
Isabel
I
Maleno
Miguel Angel
MA
López-Nevot
Teresa
T
Cabrera
José
J
Salinero
Federico
F
Garrido
D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006680:HLA Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000276:immunology*; D019656:Loss of Heterozygosity; D001613:beta 2-Microglobulin / Q000032:analysis / Q000235:genetics
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D006684:HLA-DR Antigens; D001613:beta 2-Microglobulin