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Numerical aberrations of chromosome 1 in cervical intraepithelial neoplasia are strongly associated with infection with high‐risk human papillomavirus types
Author(s) -
Bulten Johan,
Melchers Willem JG,
KooySmits Maria M,
de Wilde Peter CM,
Poddighe Pino J,
Robben Johanna CM,
Macville Merryn VE,
Massuger Leon FAG,
Bakkers Judith MJE,
Hanselaar Antonius GJM
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1222
Subject(s) - tetrasomy , cervical intraepithelial neoplasia , aneuploidy , chromosome , fluorescence in situ hybridization , intraepithelial neoplasia , in situ hybridization , biology , polymerase chain reaction , epithelium , pathology , cancer , cervical cancer , medicine , gene , genetics , prostate , gene expression
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. Copyright © 2002 John Wiley & Sons, Ltd.