6th ESACP Congress, Heidelberg, April 7-11, 1999

A041
DECREASED MIB1-EXPRESSION IN ATROPHIC CERVICAL EPITHELIUM FACILITATES CYTOLOGICAL DIAGNOSIS OF SMEARS FROM POST-MENOPAUSAL WOMEN
Bulten J 1, Wienk S 1, van der Laak J 1, Schijf Ch 2, Poddighe P 3, de Wilde P 1, Hanselaar A 1

(1) Institute of Pathology, University Hospital Nijmegen,
(2) Dept. of Gynaecology and Obstetrics, University Hospital Nijmegen,
(3) Clinical Genetics Center, University Hospital Utrecht, The Netherlands.

In Pap smears from post-menopausal women it is often difficult to distinguish atrophic epithelium from high-grade CIN. We investigated whether quantitative immunohistochemical analysis for proliferation marker Ki-67, using monoclonal antibody MIB1, would be a valuable diagnostic tool. In a training-set the proliferation activity was assessed on histological sections of 12 normal cases, 10 cases with cervical atrophy, and 10 cases with high-grade CIN (5 CIN2 and 5 CIN3). Quantitative image analysis was used to determine the MIB1 labeling index and to measure the localisation of proliferating cells in the epithelium. Preceding Pap smears were restained with MIB1,and a point-counting procedure was developed to quantify the proliferation activity index (PAI) in these smears. In addition, the point-counting procedure was used to measure the PAI in a test-set, consisting of 25 atrophies, 10 CIN2Ęs, and 16 CIN3Ęs. In cervical atrophy, the proliferation activity was significantly lower than in normal epithelium (p<0.001), whereas in high-grade CIN the proliferation activity was significantly higher than in normal epithelium (p<0.0001). Discriminant analysis resulted in a classifier for biopsy specimens and Pap smears. In the training-set, application of the two classifiers resulted in 100% correct classifications in atrophy and high-grade CIN. In the test-set, the classifier for MIB1 restained Pap smears resulted also in 100% correct classifications. We conclude that the measurement of the proliferation activity in biopsy specimens and cervical smears is a very high specific and sensitive technique to discriminate between cervical atrophy and high-grade CIN lesions.