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 epithelia in the prediction of high-grade dysplasia and to compare it with a strategy based on human papillomavirus testing.


METHODS
Our prospective study subjects were from a cohort of 498 women with minimally abnormal Papanicolaou test results including atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion who had documented repeated Papanicolaou and human papillomavirus tests. Of these, 52 eligible patients having conizations or hysterectomies as their histologic outcomes were subjected to tests of loss of heterozygosity on a panel of 5 microsatellites (D3S1110, THRB, D3S1228, D6S291, D3S1289) within the deoxyribonucleic acid of exfoliated cervical epithelia. These genetic alterations were analyzed through fluorescence polymerase chain reaction by comparison of allele ratios of exfoliated cells with those of normal control tissue. Predictive values for high-grade cervical dysplasia and cancer between this deoxyribonucleic acid marker and human papillomavirus status were compared.


RESULTS
With the use of loss of heterozygosity in at least one locus for predicting high-grade cervical neoplastic lesion, the sensitivity, specificity, 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 papillomavirus test (80%, 59.1%, 72.7%, and 92.9%). As a triage for atypical squamous cells of undetermined significance, its sensitivity and negative predictive value were up to 100%.


CONCLUSIONS
The promising results on determining microsatellite alteration in dysplastic lesions might imply that it is possible to detect the earliest changes by potential molecular markers with exfoliated cervical epithelial cells.
Chang
C L
CL
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Rd., Taipei 104, Taiwan.
Wang
S Y
SY
Wu
C C
CC
Su
T H
TH
Wang
K L
KL
Chen
H S
HS
Yang
Y C
YC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002584:Cervix Uteri / Q000737:chemistry*; D004247:DNA / Q000032:analysis* / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D004848:Epithelium / Q000737:chemistry; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000821:virology; D014626:Vaginal Smears
D004279:DNA, Viral; D004247:DNA