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 Northern China, have a very high incidence of esophageal squamous cell carcinoma (SCC). Previous studies from these counties have suggested that increased 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 these 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 collected from symptom-free subjects in Huixian. Of these, 23 esophageal biopsies were incubated with BrdU. The avidin-biotin-peroxidase complex (ABC) method was used to detect PCNA, Ki-67, and BrdU. The number of immunostain-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 esophageal biopsies, both PCNA and Ki-67 increased significantly as the epithelia 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 incorporation in the same category of BCH. With cardia biopsies, the number of Ki-67 positive cells was lower in normal tissue and increased significantly from chronic superficial gastritis to chronic atrophic gastritis to DYS. Staining patterns for PCNA and Ki-67 were correlated with the histopathology of the esophagus. The correlation was not as clear with gastric cardia. BrdU studies appear to be more complicated. The PCNA and Ki-67 methods may be useful for screening high-risk esophageal and gastric cardia cancer subjects, and for monitoring chemoprevention effects.