title: High level of aneuploidy of chromosome 6 by FISH analysis of head and neck squamous cell carcinoma: limited applicability of LOH analysis to define HLA loss.
abstract: Human Leukocyte Antigen (HLA) class I molecules are essential for tumor cell recognition by cytotoxic T cells of the adaptive immune system. Loss of HLA expression provides tumor cells with an escape mechanism to evade the immune system and thus immune therapy. Therefore, HLA loss, and in particular loss of heterozygosity (LOH), is frequently studied in tumors using microsatellite marker LOH analysis. Because LOH analysis detects any allelic imbalance and not just allelic loss, we evaluated the LOH analysis in nine head and neck squamous cell carcinomas (HNSCCs) using fluorescence in situ hybridization (FISH). These tumors were selected from 53 HNSCCs based upon the HLA class I immunohistochemical staining and LOH data. FISH analysis showed that only two tumors with LOH and one without LOH indeed had loss and a normal chromosome 6 copy number, respectively. Strikingly, for the remaining six tumors, LOH analysis did not reflect the genome HLA copy number. We demonstrated that LOH analysis cannot distinguish loss from gain and that the HLA region is not homogeneously affected within a tumor. Tumor heterogeneity and complex aneuploidy in tumors hinder a straightforward interpretation of microsatellite marker analysis. For immune therapy strategies in cancer patients, knowledge of the HLA expression on tumor cells is essential, to which LOH analysis has a limited contribution.
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands. G.Koene@azu.nl
authors.forename: Geert J P A
authors.initials: GJ
authors.lastname: Koene
authors.forename: Yvonne H A
authors.initials: YH
authors.lastname: Arts-Hilkes
authors.forename: Anette J G
authors.initials: AJ
authors.lastname: van Dijk
authors.forename: Kevin J W
authors.initials: KJ
authors.lastname: van der Ven
authors.forename: Piet J
authors.initials: PJ
authors.lastname: Slootweg
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
authors.forename: Marcel G J
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D000782:Aneuploidy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D018628:Gene Dosage; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats
chemical_list: D006680:HLA Antigens