Proton pump inhibitors reduce cell cycle abnormalities in Barrett's esophagus

Neoplastic progression in Barrett's esophagus is a multistep process in whi ch the metaplastic columnar epithelium sequentially evolves through a metap lasia-dysplasia-carcinoma sequence. The expression and DNA copy number of k ey cell cycle regulatory genes in paired normal and Barrett's esophagus sam ples was evaluated. Protein levels were evaluated in 60 formalin-fixed, par affin-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mu cosal samples expressed the p27(kip1) protein, but did not display apprecia ble nuclear staining for p16(kip4), p22(cip1) or cyclins DI and E. Barrett' s metaplastic specimens displayed increased expression levels of p16(kip4) (74%), p21(cip1) (89%) and cyclins DI (43%) and E (37%). p27 protein was ab sent in three cases. There was a significant correlation between the expres sion of p16(kip4) and cyclin E, and p21(cip1) and p27(kip4) with cyclin D1. DNA analysis did not reveal any amplification or deletion of these genes. Acid suppression, however, was associated with significantly lower expressi on levels of key cell cycle proteins. Increased expression of key cell cycl e regulatory genes appears to occur early in the neoplastic progression ass ociated with Barrett's esophagus. Treatment with proton pump inhibitors app ears to alter this increased expression.