Differentiation and proliferation in Barrett's esophagus and the effects of acid suppression.
OBJECTIVE
Maintenance of normal epithelial differentiation and proliferation is an important goal in cancer chemoprevention. Because acid has a dynamic effect on cell proliferation/differentiation of Barrett's esophagus (BE) ex vivo, we investigated the relationship between differentiation, proliferation, and dysplasia in BE biopsy specimens and explored the role of normalization of intraesophageal pH in altering the BE phenotype.


METHODS
Endoscopic biopsy specimens of BE (with or without dysplasia) were analyzed for (1) villin, a differentiation marker, by immunoblotting; (2) proliferating cell nuclear antigen (PCNA), a proliferation marker, by immunohistochemistry; and (3) dysplasia by histology before and after 6 months of normalization of intraesophageal pH (confirmed by 24-hour pH monitoring) with lansoprazole.


RESULTS
At baseline, there was a negative correlation (r = -0.79) between villin and PCNA expression. Six months later, PCNA expression decreased and villin expression increased (P < 0.001) in 24 patients whose intraesophageal pH normalized. Fifteen patients had persistently pathological intraesophageal acid reflux and no change in villin or PCNA expression. There were no differences in the occurrence of dysplasia after 6 months in either group.


CONCLUSIONS
In BE, there is an inverse relationship between villin and PCNA. In turn, dysplasia is unrelated to villin expression and well correlated with PCNA expression. Complete symptom eradication with lansoprazole does not guarantee normalization of intraesophageal pH profile in BE patients. Effective intraesophageal acid suppression favors differentiation and decreases proliferation. The intriguing possibility that acid suppression can be used to prevent dysplasia remains to be explored.
Gastroenterology Section, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA.
R
R
Ouatu-Lascar
R C
RC
Fitzgerald
G
G
Triadafilopoulos
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007150:Immunohistochemistry; D064747:Lansoprazole; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D002352:Carrier Proteins; D008840:Microfilament Proteins; D018809:Proliferating Cell Nuclear Antigen; C026615:villin; D064747:Lansoprazole; D009853:Omeprazole