ESOPHAGEAL AND GASTRIC CARDIA EPITHELIAL-CELL PROLIFERATION IN NORTHERN CHINESE SUBJECTS LIVING IN A HIGH-INCIDENCE AREA

Linxian and the nearby county Huixian, in the Henan province in Northe rn China, have a very high incidence of esophageal squamous cell carci noma (SCC). Previous studies from these counties have suggested that i ncreased proliferation of esophageal epithelial cells, morphologically manifested as basal cell hyperplasia (BCH) and dysplasia (DYS), is an early indicator of abnormality in persons predisposed to SCC. A high incidence of gastric cardia adenocarcinoma (AC) was also found in thes e areas. To determine proliferation patterns of esophageal and gastric cardia epithelia with normal and different severities of precancerous lesions, we measured proliferating cell nuclear antigen (PCNA), Ki-67 , and bromodeoxyuridine (BrdU) incorporation and compared the results. Esophageal biopsies (175) and gastric cardia biopsies (41) were colle cted from symptom-free subjects in Huixian. Of these, 23 esophageal bi opsies were incubated with BrdU. The avidin-biotin-peroxidase complex (ABC) method was used to detect PCNA, Ki-67, and BrdU. The number of i mmunostain-positive cells was counted manually. Intense immunostaining for PCNA, Ki-67, and BrdU was observed in the cell nuclei of tissues with normal and different severities of precancerous lesions. With eso phageal biopsies, both PCNA and Ki-67 increased significantly as the e pithelia progressed from normal to BCH and to DYS. The number of PCNA- and Ki-67-positive cells was three times higher than that of BrdU inco rporation in the same category of BCH. With cardia biopsies, the numbe r of Ki-57 positive cells was lower in normal tissue and increased sig nificantly from chronic superficial gastritis to chronic atrophic gast ritis to DYS. Staining patterns for PCNA and Ki-67 were correlated wit h the histopathology of the esophagus. The correlation was not as clea r with gastric cardia. BrdU studies appear to be more complicated. The PCNA and Ki-67 methods may be useful for screening high-risk esophage al and gastric cardia cancer subjects, and for monitoring chemoprevent ion effects. (C) 1998 Wiley-Liss, Inc.