title: Mutation in the beta 2m gene is not a frequent event in head and neck squamous cell carcinomas.
abstract: In cryostat sections of 84 head and neck squamous cell carcinomas (HNSCC) HLA class I and beta 2m expression was analysed using monomorphic and locus specific monoclonal antibodies. Loss of expression was heterogeneous and none of the tumours tested showed a total loss of HLA class I and/or beta 2m when analysed with W6/32, which recognises HLA class I determinants and anti-beta 2m MoAbs. Weak HLA class I and beta 2m expression was found in 9 tumours (11%) and heterogeneous expression was found in 2 tumours (2%). When analysed with locus-specific antibodies (HCA2 and HC10, anti-HLA-A and anti-HLA-B/C, respectively) 37 tumours (44%) showed a loss, weak or heterogeneous expression of one or both loci. Tumours showing a down-regulated HLA class I expression were analysed for mutations in either allele of the beta 2m gene by sequencing based mutation analysis (SBMA). Exon 1 and exons 2 and 3 were amplified separately by PCR using M13-tailed intron-specific primers. PCR products were sequenced in two directions. In none of the tumours mutations in the beta 2m gene were detected. In 59% of the tumours with down-regulated HLA class I expression, lost or down-regulated TAP 1 expression was found when analysed with anti-TAP 1 antibodies. This indicates an important role for TAP in down-regulation of HLA class I expression in HNSCC.
authors.affiliation: Department of Pathology, University Hospital, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Feenstra
authors.forename: E
authors.initials: E
authors.lastname: Rozemuller
authors.forename: K
authors.initials: K
authors.lastname: Duran
authors.forename: I
authors.initials: I
authors.lastname: Stuy
authors.forename: J
authors.initials: J
authors.lastname: van den Tweel
authors.forename: P
authors.initials: P
authors.lastname: Slootweg
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; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004273:DNA, Neoplasm; D015536:Down-Regulation; D005091:Exons; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin