Ouatu-Lascar R, Fitzgerald R C, Triadafilopoulos G
Gastroenterology Section, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA.
Gastroenterology. 1999 Aug;117(2):327-35. doi: 10.1053/gast.1999.0029900327.
BACKGROUND & AIMS: 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.
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.
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.
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.
维持正常上皮分化和增殖是癌症化学预防的一个重要目标。由于酸对巴雷特食管（BE）细胞增殖/分化具有动态影响，我们研究了BE活检标本中分化、增殖和发育异常之间的关系，并探讨了食管内pH值正常化在改变BE表型中的作用。
对BE（有或无发育异常）的内镜活检标本进行以下分析：（1）通过免疫印迹法检测绒毛蛋白（一种分化标志物）；（2）通过免疫组织化学检测增殖细胞核抗原（PCNA，一种增殖标志物）；（3）在使用兰索拉唑使食管内pH值正常化6个月（通过24小时pH监测确认）前后，通过组织学检查发育异常情况。
基线时，绒毛蛋白和PCNA表达呈负相关（r = -0.79）。6个月后，食管内pH值正常化的24例患者中，PCNA表达下降，绒毛蛋白表达增加（P < 0.001）。15例患者食管内持续存在病理性酸反流，绒毛蛋白或PCNA表达无变化。两组6个月后发育异常的发生率无差异。
在BE中，绒毛蛋白和PCNA呈负相关。反过来，发育异常与绒毛蛋白表达无关，与PCNA表达密切相关。使用兰索拉唑完全消除症状并不能保证BE患者食管内pH值曲线正常化。有效的食管内酸抑制有利于分化并减少增殖。酸抑制可用于预防发育异常这一有趣的可能性仍有待探索。
