Angelique Levert-Mignon1, Michael J Bourke2, Sarah J Lord3, Andrew C Taylor4, Antony R Wettstein5, Melanie Edwards6, Natalia K Botelho1, Rebecca Sonson2, Chatura Jayasekera4, Oliver M Fisher1, Melissa L Thomas3, Finlay Macrae7, Damian J Hussey8, David I Watson8, Reginald V Lord9. 1. Gastroesophageal Cancer Research Program, St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia. 2. Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, NSW, Australia. 3. Gastroesophageal Cancer Research Program, St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia; School of Medicine, University of Notre Dame, Sydney, NSW, Australia. 4. Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia. 5. Diagnostic Endoscopy Centre, St Vincent's Clinic, Sydney, NSW, Australia. 6. School of Medicine, University of Notre Dame, Sydney, NSW, Australia; Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, NSW Australia. 7. Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Medicine, The University of Melbourne, Parkville, VIC, Australia. 8. Department of Surgery, Flinders University, Flinders Medical Centre Bedford Park, SA, Australia; Flinders Centre for Cancer Prevention and Control, Flinders University, Bedford Park, SA, Australia. 9. Gastroesophageal Cancer Research Program, St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia; School of Medicine, University of Notre Dame, Sydney, NSW, Australia; Diagnostic Endoscopy Centre, St Vincent's Clinic, Sydney, NSW, Australia.
Abstract
BACKGROUND: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). OBJECTIVE: The purpose of this study was to investigate the molecular effects of endotherapy. METHODS: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. RESULTS: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. CONCLUSION: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more "normal" profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.
BACKGROUND: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). OBJECTIVE: The purpose of this study was to investigate the molecular effects of endotherapy. METHODS: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. RESULTS: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. CONCLUSION: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more "normal" profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.
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