Distinct cytogenetic alterations in squamous intraepithelial lesions of the cervix revealed by laser-assisted microdissection and comparative genomichybridization

BACKGROUND, It has been established that comparative genomic hybridization (CGH) on Papanicolaou-stained cervical smears can be used to identify chrom osomal imbalances, METHODS. In this study, the authors identified normal and dysplastic squamo us epithelial cells cytologically: eliminated surrounding bacteria or leuko cytes by a ultraviolet laser microbeam under microscopic control, and scrap ed out the cell groups of interest by a microdissection system. In 3 cases of squamous intraepithelial lesions (SIL), a total of 9 samples of dysplast ic (n = 6) and nontumorous cells (n = 3) were investigated, each of them co nsisting of 3-40 cells. The DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and used for CGH. RESULTS, Analyses of all nontumorous cell groups resulted in fluorescence r atio profiles that showed no deviation from the normal range, confirming th at no methodologic artefacts have been produced. The CGH profiles from dysp lastic cells, however, showed various chromosomal imbalances affecting six to nine different chromosomes. The most frequent gains in DNA were observed on chromosomes 1p, 2q, 4, and 5, whereas losses were found on chromosomes 6q and 13q. CONCLUSIONS. The results of this study demonstrate the feasibility and reli ability of CGH on microdissected cell samples of routinely processed cervic al smears. To the authors' knowledge, this is the first study reporting the use of CGH on cervical routine smears. This approach offers the opportunit y to investigate sequence copy number changes in small, morphologically wel l-defined groups of dysplastic cells. It may, therefore, serve as a cytogen etic screening test for identifying chromosomal aberrations in precancerous lesions that are associated with a high risk for progression to invasive c ancer. Cancer (Cancer Cytopathol) 1998;84:375-9. (C) 1998 American Cancer S ociety.