title: Multiparameter DNA flow-sorting demonstrates diploidy and SDHD wild-type gene retention in the sustentacular cell compartment of head and neck paragangliomas: chief cells are the only neoplastic component.
abstract: Head and neck paragangliomas are considered to be biphasic tumours, composed of two distinct cell types: chief cells and sustentacular cells. A substantial number of these tumours show mutations in the SDHD gene located at chromosome 11q23. Although there is general agreement that paragangliomas are a neoplastic proliferation of chief cells, the nature of sustentacular cells is still a matter of debate. To clarify the nature of sustentacular cells further, multiparameter DNA flow cytometry was performed utilizing S-100 labelling as a selective marker of the sustentacular fraction simultaneously with DNA content measurement in six head and neck paragangliomas. S-100-positive fractions and other tumour-cell populations were flow-sorted and restriction digestion analysis of SDHD mutations was performed on each fraction. Flow cytometry demonstrated that the S-100 labelled cells were diploid. Restriction digestion analysis in informative cases revealed retention of the wild-type SDHD allele in S-100-positive fractions and loss of the wild-type allele in S-100-negative fractions. These data strongly suggest that sustentacular cells should be regarded as a non-neoplastic cell population that may be induced as a tumour-specific stromal component by chief cells.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Pieter B
authors.initials: PB
authors.lastname: Douwes Dekker
authors.forename: Willem E
authors.initials: WE
authors.lastname: Corver
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Andel G L
authors.initials: AG
authors.lastname: van der Mey
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Cornelisse
mesh_terms: D022981:Allelic Imbalance; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000378:metabolism; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D009418:S100 Proteins / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009418:S100 Proteins; D013385:Succinate Dehydrogenase