Numerical aberrations of chromosome 1 in cervical intraepithelial neoplasia are strongly associated with infection with high-risk human papillomavirus types.
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.
Bulten
Johan
J
Department of Pathology, University Medical Center, Nijmegen, The Netherlands. H.Bulten@Pathol.azn.nl
Melchers
Willem J G
WJ
Kooy-Smits
Maria M
MM
de Wilde
Peter C M
PC
Poddighe
Pino J
PJ
Robben
Johanna C M
JC
Macville
Merryn V E
MV
Massuger
Leon F A G
LF
Bakkers
Judith M J E
JM
Hanselaar
Antonius G J M
AG
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