PROLIFERATION AND DNA ANEUPLOIDY IN MILD DYSPLASIA IMPLY EARLY STEPS OF CERVICAL CARCINOGENESIS

This project was focused on cellular proliferation relative to the ons et of endoreplication and effects of DNA aneuploidy during carcinogene sis in cervical mucosa. Proliferation was monitored with MIBI antibody , whereas nuclear DNA content was quantified using an image processing microphotometer. For the later procedure, 8 mu m sections were of ade quate depth with interphases, and lymphocyte nuclei provided an intern al standard of the diploid (2c) DNA content. Results from 95 cervical biopsies displaying different types of dysplasia and carcinoma were su pplemented with those of cervical smears from 319 cases. The later spe cimens had been selected from about 30 000 consecutive cases in 1993/9 4. MIB1-traced proliferation was found in the second cell layer, where as the bulk of basal cells remained quiescent in normal mucosa. Howeve r, predominant MIBI immunoreactivity was observed with endoreplicated nuclei. A critical 30% of the cases exhibited DNA aneuploidy already i n mild dysplasia, which was found in cytological smears and histologic al sections. The nuclear DNA content of basal cells increased progress ively by endoreplication corresponding to the degree of dysplasia. Cas es of carcinoma in situ displayed some 18% of non-proliferating diploi d cells despite overwhelming endoreplication and DNA aneuploidy. High MIB1 levels combined with DNA aneuploidy unambiguously indicate the be ginning of cervical carcinogenesis. The limits of the Bethesda system were discussed.