Epithelial cell proliferative activity of Barrett's esophagus: methodology and correlation with traditional cancer risk markers

Barrett's esophagus (BE) is a premalignant condition, due to chronic gastroesophageal reflux. Effective antireflux therapy may diminish cancer risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferative activity of Barrett's mucosa as an intermediate marker and correlated the activity with traditional cancer risk markers and other parameters. Fifty-six patients (21-74 years of age) with Barrett's esophagus and established acid gastroesophageal reflux were included. Biopsies were taken from Barrett's mucosa at 3-cm intervals. Reflux was measured by 24-hr pH-metry. Proliferative activity was determined using in vitro labeling with 5-bromodeoxyuridine and immunohistochemistry and was expressed as labeling index (LI). The length of BE correlated with erect acid reflux (P = 0.002). LI in specialized columnar metaplasia was higher than in gastric metaplasia, especially in crypt epithelium (P <0.05). Multiple regression analysis revealed independent positive correlations for surface LI with dysplasia (P 0.011), distance from the incisors (P = 0.041), and crypt LI (P = 0.000). Crypt LI showed an independent positive correlation with the length of BE (P = 0.033) and type of metaplasia (P = 0.007). In conclusion, epithelial cell proliferative activity of BE correlates with several known risk factors for cancer. Proliferative activity is an attractive intermediate marker to evaluate the effects of interventional measures to decrease cancer risk in Barrett's esophagus.