title: Improved cervical smear assessment using antibodies against proteins that regulate DNA replication.
abstract: Carcinoma of the cervix is one of the most common malignancies. Papanicolaou (Pap) smear tests have reduced mortality by up to 70%. Nevertheless their interpretation is notoriously difficult with high false-negative rates and frequently fatal consequences. We have addressed this problem by using affinity-purified antibodies against human proteins that regulate DNA replication, namely Cdc6 and Mcm5. These antibodies were applied to sections and smears of normal and diseased uterine cervix by using immunoperoxidase or immunofluorescence to detect abnormal precursor malignant cells. Antibodies against Cdc6 and Mcm5 stain abnormal cells in cervical smears and sections with remarkably high specificity and sensitivity. Proliferation markers Ki-67 and proliferating cell nuclear antigen are much less effective. The majority of abnormal precursor malignant cells are stained in both low-grade and high-grade squamous intraepithelial lesions. Immunostaining of cervical smears can be combined with the conventional Pap stain so that all the morphological information from the conventional method is conserved. Thus antibodies against proteins that regulate DNA replication can reduce the high false-negative rate of the Pap smear test and may facilitate mass automated screening.
authors.affiliation: Wellcome Trust/Cancer Research Campaign Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom. ks247@hermes.cam.ac.uk
authors.forename: G H
authors.initials: GH
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Romanowski
authors.forename: L
authors.initials: L
authors.lastname: Morris
authors.forename: M
authors.initials: M
authors.lastname: Madine
authors.forename: A D
authors.initials: AD
authors.lastname: Mills
authors.forename: K
authors.initials: K
authors.lastname: Stoeber
authors.forename: J
authors.initials: J
authors.lastname: Marr
authors.forename: R A
authors.initials: RA
authors.lastname: Laskey
authors.forename: N
authors.initials: N
authors.lastname: Coleman
mesh_terms: D000906:Antibodies; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D018797:Cell Cycle Proteins / Q000276:immunology; D004261:DNA Replication / Q000276:immunology*; D004268:DNA-Binding Proteins; D005260:Female; D005656:Fungal Proteins / Q000276:immunology; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D008403:Mass Screening / Q000379:methods; D065006:Papanicolaou Test; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D014626:Vaginal Smears / Q000379:methods*
chemical_list: D000906:Antibodies; C066503:CDC6 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D019394:Ki-67 Antigen; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C085711:mcm5 protein, S pombe