title: HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas.
abstract: Loss at the chromosomal region 6p21.3 is a frequent event in head and neck squamous cell carcinomas (HNSCC). Since the human leukocyte antigen (HLA) complex is located at 6p21.3, loss of heterozygosity (LOH) of this region may provide tumour cells with an immune-escape tumour phenotype. In the present study, we have studied the correlation of HLA class I, TAP1 and TAP2 expression and LOH at 6p21.3. HLA class I and TAP1 and TAP2 protein expression was analysed by immunohistochemical procedures. A panel of 41 HNSCC with downregulated HLA class I expression was selected for LOH studies using 5 microsatellite markers located at 6p21.3 (D6S105, D6S265, D6S276, D6S273, D6S291) and 2 markers located at the chromosome 6 centromere (D6S473) and the 6p telomere (D6S277). In addition, LOH of the beta-2-nmicroglobulin (beta2m) gene was studied using 2 microsatellite markers flanking the beta2m gene (D15S126 and D15S153) and was correlated with beta2m and HLA class I expression. In 20/41 (49%) of the HNSCC, allelic loss for at least one locus at 6p21.3 was found. Loss at 15q was found in 4/10 (40%) HNSCC with downregulated beta2m expression and in 12/41 (29%) HNSCC with downregulated HLA class I expression. Our data show that downregulation of HLA class I expression is correlated with loss of chromosomal regions at 6p21.3 in HNSCC. In addition, LOH at 6p21.3 and 15q in 10 paired samples of DNA derived from the primary HNSCC, the lymph node metastases and from peripheral blood lymphocytes (PBLs) was studied. Five (5/10) primary tumours contained the same deletion as the corresponding lymph node metastases. The other cases contained deletions either in the primary tumour (3 cases) or in the lymph node metastases (1 case) or no deletions at all (1 case).
authors.affiliation: Department of Pathology, University Hospital, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Feenstra
authors.forename: M
authors.initials: M
authors.lastname: Veltkamp
authors.forename: J
authors.initials: J
authors.lastname: van Kuik
authors.forename: S
authors.initials: S
authors.lastname: Wiertsema
authors.forename: P
authors.initials: P
authors.lastname: Slootweg
authors.forename: J
authors.initials: J
authors.lastname: van den Tweel
authors.forename: R
authors.initials: R
authors.lastname: de Weger
authors.forename: M
authors.initials: M
authors.lastname: Tilanus
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D002896:Chromosomes, Human, Pair 6; D003593:Cytoplasm / Q000737:chemistry; D004273:DNA, Neoplasm; D006680:HLA Antigens / Q000096:biosynthesis*; D015234:HLA-A Antigens / Q000096:biosynthesis / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity / Q000235:genetics; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008285:Major Histocompatibility Complex; D018895:Microsatellite Repeats; D019680:Trinucleotide Repeat Expansion; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D004273:DNA, Neoplasm; D006680:HLA Antigens; D015234:HLA-A Antigens; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; C071692:TAP2 protein, human