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 (original) (raw)
Abstract.
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.
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Authors and Affiliations
- Departamento de Análisis Clínicos, Hospital UniversitarioVirgen de las Nieves, Universidad de Granada, Avd. Fuerzas Armadas 2, 18014 Granada, Spain
Isabel Maleno, Miguel López-Nevot, Teresa Cabrera & Federico Garrido - Departamento de Otorrinolaringología, Hospital UniversitarioVirgen de las Nieves, Universidad de Granada, 18014 Granada, Spain
José Salinero
Authors
- Isabel Maleno
- Miguel López-Nevot
- Teresa Cabrera
- José Salinero
- Federico Garrido
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Maleno, I., López-Nevot, M., Cabrera, T. et al. 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.Cancer Immunol Immunother 51, 389–396 (2002). https://doi.org/10.1007/s00262-002-0296-0
- Received: 14 March 2002
- Accepted: 18 April 2002
- Published: 28 June 2002
- Issue date: September 2002
- DOI: https://doi.org/10.1007/s00262-002-0296-0