MARKERS OF CELL-PROLIFERATION IN NORMAL EPITHELIA AND DYSPLASTIC LEUKOPLAKIAS OF THE ORAL CAVITY

The expression of several markers of epithelial cell proliferation was analyzed to establish baseline data for future chemoprevention studie s of oral premalignant lesions. Punch biopsies (n = 60) from three dif ferent sites of oral mucosa (bucca, lateral tongue, and the floor of t he mouth) were obtained from 20 normal donors of both sexes, After for maldehyde fixation and paraffin embedding, immunohistochemistry was us ed to detect the proliferation markers Mib-1, cyclin D1, and centromer e-associated protein CENP-F, Analysis of sections stained for the thre e markers showed similar patterns, i,e,, a low labeling index (LI) in the basal layer and a high LI in the parabasal layer at all three intr aoral sites, No proliferative activity was seers above the parabasal l ayer (superficial layer). All sites showed similar Mib-1 LI values for the proliferative markers. The tongue epithelium exhibited higher par abasal LIs of cyclin D1 and CENP-F than did the other two sites. No si gnificant differences were detected between smokers and nonsmokers. Th e data from normal mucosa were compared with those from low (n = 30)- and high (n = 17)-grade dysplastic leukoplakias. The Mib-1 LI showed a very significant change, with a 9-fold increase in the basal layer LI in dysplastic leukoplakias, Cyclin D1 and CENP-F showed similar trend s with increments of up to 7-fold in the basal layer of high-grade dys plasia, Although the proliferative activity of the parabasal layer was similar in normal and leukoplakic epithelia, the superficial layer sh owed a significant increment in proliferative activity mainly in high- grade leukoplakia, These studies suggest that proliferation markers in the basal and superficial cells of premalignant lesions may serve as surrogate end point biomarkers for chemoprevention trials.