EPITHELIAL-CELL PROLIFERATIVE ACTIVITY OF BARRETTS-ESOPHAGUS - METHODOLOGY AND CORRELATION WITH TRADITIONAL CANCER RISK MARKERS

Barrett's esophagus (BE) is a premalignant condition, due to chronic g astroesophageal reflux. Effective antireflux therapy may diminish canc er risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferati ve activity of Barrett's mucosa as an intermediate marker and correlat ed the activity with traditional cancer risk markers and other paramet ers. Fifty-six patients (21-74 years of age) with Barrett's esophagus and established acid gastroesophageal reflux were included. Biopsies w ere taken from Barrett's mucosa at 3-cm intervals. Reflux was measured by 24-hr pH-metry. Proliferative activity was determined using in vit ro labeling with 5-bromodeoxyuridine and immunohistochemistry and was expressed as labeling index (LI). The length of BE correlated with ere ct 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 cor relations for surface LI with dysplasia (P 0.011), distance from the i ncisors (P = 0.041), and crypt LI (P = 0.000). Crypt LI showed an inde pendent positive correlation with the length of BE (P = 0.033) and typ e of metaplasia (P = 0.007). In conclusion, epithelial cell proliferat ive activity of BE correlates with several known risk factors for canc er. Proliferative activity is an attractive intermediate marker to eva luate the effects of interventional measures to decrease cancer risk i n Barrett's esophagus.