title: Numerical aberrations of chromosome 1 in cervical intraepithelial neoplasia are strongly associated with infection with high-risk human papillomavirus types.
abstract: The aims of this study were to assess the relationships between numerical aberrations of chromosome 1 and the presence of high-risk human papillomavirus (HPV). Five normal samples, 11 CIN1, 13 CIN2, 18 CIN3, and nine carcinomas were studied by in situ hybridization (ISH), using a DNA probe for the centromere of chromosome 1 (cen#1) and a DNA probe cocktail for HPV types 16 and 18. A short fragment polymerase chain reaction hybridization line probe assay (SPF-PCR-LiPA) technique was used to detect 25 HPV types. The mean number of cen#1 per nucleus (chromosome index, CI) was measured, and the fractional areas of dysplastic epithelium with HPV16/18 infection and with cen#1 aneusomy were estimated. Disomy was found in all normal epithelium and in 36% of CIN1. Tetrasomy was observed in 64% of CIN1, 15% of CIN2, and 17% of CIN3. Hyper-tetrasomy was observed in 77% of CIN2, 83% of CIN3, and 100% of invasive carcinomas. High-risk HPVs were present in 20%, 75%, and 94% of disomic, tetrasomic, and hyper-tetrasomic lesions, respectively. The mean CI value was significantly higher in the lesions infected with high-risk HPV than in the lesions not infected by high-risk HPV (p < 0.001), due to the significantly higher prevalence of hyper-tetrasomy. The ISH study disclosed that HPV16/18 was exclusively found within dysplastically altered epithelium. The area with aneusomy is mostly enclosed within the area infected with HPV. In 83% of the HPV16/18-positive CIN lesions, the fractional area of HPV-infected epithelium was equal to, or larger than, the fractional area with aneusomy. In conclusion, aneusomy for chromosome 1 is strongly associated with high-grade CIN lesions and infection with high-risk HPV; it is likely that the occurrence of numerical aberrations of chromosome 1 is preceded by infection with high-risk HPV.
authors.affiliation: Department of Pathology, University Medical Center, Nijmegen, The Netherlands. H.Bulten@Pathol.azn.nl
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
authors.forename: Maria M
authors.initials: MM
authors.lastname: Kooy-Smits
authors.forename: Peter C M
authors.initials: PC
authors.lastname: de Wilde
authors.forename: Pino J
authors.initials: PJ
authors.lastname: Poddighe
authors.forename: Johanna C M
authors.initials: JC
authors.lastname: Robben
authors.forename: Merryn V E
authors.initials: MV
authors.lastname: Macville
authors.forename: Leon F A G
authors.initials: LF
authors.lastname: Massuger
authors.forename: Judith M J E
authors.initials: JM
authors.lastname: Bakkers
authors.forename: Antonius G J M
authors.initials: AG
authors.lastname: Hanselaar
mesh_terms: D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D014412:Tumor Virus Infections / Q000150:complications / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology