Microsatellite alterations in exfoliated cervical epithelia deoxyribonucleic acid as a marker for high-grade dysplasia

OBJECTIVE: The purpose of this study was to evaluate the feasibility of the use of deoxyribonucleic acid microsatellite alterations in cervical epithe lia in the prediction of high-grade dysplasia and to compare it with a stra tegy based on human papillomavirus testing. STUDY DESIGN: Our prospective study subjects were from a cohort of 498 wome n with minimally abnormal Papanicolaou test results including atypical squa mous cells of undetermined significance and low-grade squamous intraepithel ial lesion who had documented repeated Papanicolaou and human papillomaviru s tests. Of these, 52 eligible patients having conizations or hysterectomie s as their histologic outcomes were subjected to tests of loss of heterozyg osity on a panel of 5 microsatellites (D3S1110, THRB, D3S1228, D6S291, D3S1 289) within the deoxyribonucleic acid of exfoliated cervical epithelia. The se genetic alterations were analyzed through fluorescence polymerase chain reaction by comparison of allele ratios of exfoliated cells with those of n ormal control tissue. Predictive values for high-grade cervical dysplasia a nd cancer between this deoxyribonucleic acid marker and human papillomaviru s status were compared. RESULTS: With the use of loss of heterozygosity in at least one locus for p redicting high-grade cervical neoplastic lesion, the sensitivity, specifici ty, positive predictive value, and negative predictive value were 96.7%, 59 .1%, 76.3%, and 92.9%, which were superior to those of the human papillomav irus test (80%, 59.1%, 72.7%, and 92.9%). As a triage for atypical squamous cells of undetermined significance, its sensitivity and negative predictiv e value were up to 100%. CONCLUSION: The promising results on determining microsatellite alteration in dysplastic lesions might imply that it is possible to detect the earlies t changes by potential molecular markers with exfoliated cervical epithelia l cells.