title: Decreased expression of Ki-67 in atrophic cervical epithelium of post-menopausal women.
abstract: Papanicolaou-stained cervical smears (Pap smears) of post-menopausal women often present difficulties in distinguishing atrophic cervical epithelium from high-grade cervical intraepithelial neoplasia (CIN2-3). The aim of this study was to disclose differences in proliferative activity in normal cervical epithelium, cervical atrophy, and high-grade CIN lesions, in order to develop specific and sensitive classifiers to discriminate between cervical atrophy and high-grade CIN, both in cervical smears and in tissue sections. A case-control study was done on 83 patients. Proliferative activity was assessed in histological sections using the monoclonal antibody MIB1. An image analysis system was used to characterize different proliferation-associated features. Preceding Pap smears were restained with MIB1 and proliferative activity was measured by a point-counting procedure, carried out on a training set of 32 cases and a test set of 51 cases. In cervical atrophy, proliferative activity was significantly lower than in normal epithelium (p<0.001). Proliferative activity measured in both biopsies and cervical smears was considerably higher in high-grade CIN than in normal epithelium (p<0.001). Discriminant analyses resulted in four classifiers, based on proliferation parameters, to discriminate between cervical atrophy and high-grade CIN, and between CIN2 and CIN3, in biopsy specimens and cervical smears, respectively. The two classifiers for biopsy specimens resulted in 100% correct classification. Application of the classifier obtained from the training set of Pap smears resulted in 100% correct classification of the Pap smears in the test set. The classifier to discriminate between CIN2 and CIN3 in Pap smears, obtained from 36 patients, resulted in 87% and 90% correct classification, respectively.
authors.affiliation: Institute of Pathology, University Hospital Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Bulten
authors.forename: P C
authors.initials: PC
authors.lastname: de Wilde
authors.forename: C
authors.initials: C
authors.lastname: Schijf
authors.forename: J A
authors.initials: JA
authors.lastname: van der Laak
authors.forename: S
authors.initials: S
authors.lastname: Wienk
authors.forename: P J
authors.initials: PJ
authors.lastname: Poddighe
authors.forename: A G
authors.initials: AG
authors.lastname: Hanselaar
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001284:Atrophy / Q000175:diagnosis / Q000378:metabolism; D016022:Case-Control Studies; D002455:Cell Division; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology*; D003663:Decision Trees; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen