Reflux of duodenal juice induces esophageal carcinoma in Trp53-knockout mice

Background: Loss of p53 function enhances malignant progression. The aim wa s to evaluate whether p53 function is relevant for the development of esoph ageal carcinoma following surgically induced reflux. Methods: Total gastrectomy with esophagojejunostomy was microsurgically per formed in Trp53-knockout (Trp53(-/-)) and wild-type (WT) mice at 6 weeks of age, creating reflux of duodenal juice into the esophagus. Unoperated cont rol mice were kept under identical conditions for 24 weeks. Results: While the esophagus was normal in all unoperated mice (6 Trp53(-/- ), 10 WT), there was esophagitis of the distal part of the esophagus in all operated mice (4 Trp53(-/-), 19 WT). None of the WT mice developed dysplas ia or carcinoma. In all Trp53-knockout mice squamous dysplasia and in two c arcinoma were found. Conclusion: Reflux of duodenal juice can initiate development of esophageal cancer. Due to enhanced malignant progression dysplasia and carcinoma deve loped in Trp53-knockout mice.