title: Chromosome instability predicts progression of premalignant lesions of the larynx.
abstract: The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7. Additionally, immunostainings for p53, Cyclin D1 and (p)FADD expression were evaluated. Malignant progression was recorded. Eighteen patients with carcinoma in situ (CIS) were treated after diagnosis and excluded from follow-up. Chromosome instability was strongly associated with a high risk of malignant transformation, especially in lower grade lesions (hyperplasia, mild and moderate dysplasia; odds ratio = 8.4, p = 0.004). Patients with lesions containing chromosome instability showed a significantly worse 5-year progression-free survival than those with premalignancies without chromosome instability (p = 0.002). Neither histopathology nor the protein markers predicted progression in univariate analysis, although histopathological diagnosis, p53 and FADD contributed positively to chromosome instability in multivariate analysis. Chromosome instability is associated with malignant progression of laryngeal premalignancies, especially in lower grade lesions. These results may contribute to better risk counselling, provided that they can be validated in a larger patient set.
authors.affiliation: 1Department of Otorhinolaryngology and Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Centre 2Department of Otorhinolaryngology and Head and Neck Surgery, Atrium Medical Centre, Heerlen 3Departments of Molecular Cell Biology 4Pathology 5Epidemiology 6School for Mental Health and Neuroscience 7Department of Methodology and Statistics, Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre 8Department of Pathology, University Medical Centre Groningen, The University of Groningen, The Netherlands.
authors.forename: Verona E
authors.initials: VE
authors.lastname: Bergshoeff
authors.forename: Stijn J A
authors.initials: SJ
authors.lastname: Van der Heijden
authors.forename: Annick
authors.initials: A
authors.lastname: Haesevoets
authors.forename: Sophie G H
authors.initials: SG
authors.lastname: Litjens
authors.forename: Fredrik J
authors.initials: FJ
authors.lastname: Bot
authors.forename: Adri C
authors.initials: AC
authors.lastname: Voogd
authors.forename: Michelene N
authors.initials: MN
authors.lastname: Chenault
authors.forename: Anton H N
authors.initials: AH
authors.lastname: Hopman
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Van der Wal
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Manni
authors.forename: Frans C S
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: Bernd
authors.initials: B
authors.lastname: Kremer
authors.forename: Ernst-Jan M
authors.initials: EJ
authors.lastname: Speel
mesh_terms: D000328:Adult; D000368:Aged; D043171:Chromosomal Instability; D019938:Cyclin D1 / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D053200:Fas-Associated Death Domain Protein / Q000235:genetics; D005260:Female; D006801:Humans; D006965:Hyperplasia; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D007830:Larynx / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019938:Cyclin D1