title: LOH at 6p21.3 region and HLA class I altered phenotypes in bladder carcinomas.
abstract: Alterations in HLA class I antigen expression have been frequently described in different epithelial tumors and are thought to favor tumor immune escape from T lymphocyte recognition. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes. Some are structural defects that produce unresponsiveness to treatment with interferons. Others include alterations in regulatory mechanisms that can be switched on by treatment of tumor cells with different cytokines. One important mechanism belonging to the first group is loss of heterozygosity (LOH) at chromosome region 6p21.3, which can lead to HLA haplotype loss. In this investigation, the frequency of LOH at 6p21 chromosome region was studied in 69 bladder carcinomas. Short tandem repeat analysis showed that 35% of cases had LOH in this chromosome region. By considering these results together with immunohistological findings previously published by our group, we identified a distribution pattern of HLA class I altered phenotypes in bladder cancer. The most frequently altered phenotype in bladder carcinomas was total loss of HLA class I expression (17 cases, 25%), followed by phenotype II associated with HLA haplotype loss (12 cases, 17.5%), and HLA allelic loss (ten cases, 14.5%). Nine cases (13%) were classified as having a compound phenotype, five cases (7%) as having HLA locus loss, and in 16 cases (23%) no alteration in HLA expression was detected. An important conclusion of this report is that a combination of different molecular and immunohistological techniques is required to precisely define which HLA alleles are lost during tumor progression and to characterize the underlying mechanisms of these losses. These studies should be performed when a cancer patient is to be included in an immunotherapy protocol that aims to stimulate different immune effector mechanisms.
authors.affiliation: Dept. de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Avd. Fuerzas Armadas 2, 18014, Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Maleno
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Romero
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabrera
authors.forename: Laura
authors.initials: L
authors.lastname: Paco
authors.forename: Natalia
authors.initials: N
authors.lastname: Aptsiauri
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Cozar
authors.forename: Miguel
authors.initials: M
authors.lastname: Tallada
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Federico
authors.initials: F
authors.lastname: Garrido
mesh_terms: D000595:Amino Acid Sequence; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000276:immunology; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015870:Gene Expression; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010641:Phenotype; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000276:immunology
chemical_list: D006680:HLA Antigens