CELLULAR KINETICS IN BARRETTS EPITHELIUM CARCINOGENIC SEQUENCE - ROLES OF APOPTOSIS, BCL-2 PROTEIN, AND CELLULAR PROLIFERATION

To gain insight into the neoplastic progression of Barrett's epitheliu m (BE), we assessed the expression of Ki-67 antigen and bcl-2 protein and the occurrence of apoptosis in metaplastic epithelium with and wit hout regenerative atypia (RA), low-grade dyplasia, and high-grade dysp lasia (HGD). To refine our understanding of the epithelial kinetics du ring the carcinogenic sequence, we performed separate analyses of four different mucosal regions, i.e., surface epithelium, upper and lower crypts, and glands. Expansion of the proliferative zone was noted in d ysplasia and to a mild degree in epithelium with RA but not in BE. Exp ression of bcl-2 protein was seen in the proliferative zone in BE and showed a significant increase in RA but was essentially absent in HGD, Numerous apoptotic nuclei were seen in HGD, decreasing along the cell ular gradient from gland to surface. We noted a positive correlation b etween Ki-67 and bcl-2 in the proliferative zone of BE and RA, whereas a negative correlation was present on the surface of RA, Ki-67 was po sitively correlated with apoptosis in the lower crypts of HGD. bcl-2 e xpression was negatively correlated with apoptosis in all regions exce pt the proliferative zone of dysplastic areas. Our findings suggest th at overexpression of bcl-2 protein is not an important step in the car cinogenesis of BE. We confirm the upward shift of cellular proliferati on in dysplastic epithelia. Apoptosis that is increased in dysplasia m ight play a significant role in carcinogenesis by restraining increase d cellular proliferation.