Chromosomal Aberrations Accumulate in Polyploid cells of High-grade Squamous Intraepithelial Lesions (HSIL)

Gábor MÉHES2, Norbert SPEICH3, Magdolna BOLLMANN1, Reinhard BOLLMANN1

1Institute of Pathology, Bonn-Duisdorf, Germany
2Department of Pathology, University of Pécs, Pécs, Hungary
3Institute of Molecular Pathology and Gene Diagnostics, Bonn, Germany


Persistant infection with human papillomavirus (HPV) of the uterine cervix is related with cytological atypia (SIL), the oncogenic potential of which is unclear in a given time point of monitoring. HPVinduced genetic instability result in polyploidization as well as in low frequency random chromosome aberrations in squamous cells. In the present work we analyzed whether highly polyploid/aneuploid cells reflect genomic changes at the chromosomal level. 13 samples with the cytological diagnosis of HSIL were analyzed for HPV type and nuclear DNA content measured by laser scanning cytometry (LSC). Hyperdiploid cells with >5c and with >9c DNA content were further analyzed for numerical aberrations of the chromosomes 3 and 17 by fluorescence in situ hybridization (FISH) following repositioning. Cells with >5c DNA content were found more frequently than cells with >9c DNA content (5-98 and 1-44 cells, respectively). The FISH analysis demonstrated frequent polysomies, however, the rate of aneusomy (other than 2, 4, 8 or 16 chromosome copies) was significantly higher in cells with >9c DNA content than in cells with >5c DNA content or the normal diploid cells. The imbalance of chromosome 3 and 17 copy number was also increased in cells with >9c DNA content. Moreover, in three out of the 13 analyzed HSIL samples, recurrent abnormal chromosome 3/17 ratio was demonstrated in a significant part of the cells, indicating a common origin of these cells. Highly polyploid/aneuploid cells in HSIL accumulate cytogenetic aberrations detectable by FISH analysis. These cells may reflect early changes with tumorigenic potential in a very concentrated fashion. Pathology & Oncology Research, Vol 10, Nr 3, 142-148, 2004

Key words: HPV; aneuploidy; chromosome; cytology; cervix

Received: Jul 26, 2004; accepted: Aug 3, 2004
Correspondence: Gábor MÉHES, Department of Pathology, University of Pécs, Szigeti út 12 Pécs H-7602, Hungary; Tel: 36 72 536 001 / 1843, Fax: 36 72 536 281; E-mail:

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