Abstract
OBJECTIVE: Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett's oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance.
DESIGN: We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC).
RESULTS: We found that 58 of 77 short-segment (<3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p<0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer.
CONCLUSION: SS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance.
| Original language | English |
|---|---|
| Pages (from-to) | 729-740 |
| Number of pages | 12 |
| Journal | Gut |
| Volume | 73 |
| Issue number | 5 |
| Early online date | 21 Nov 2023 |
| DOIs | |
| Publication status | Published - 5 Apr 2024 |
Bibliographical note
Collaborators:Rebecca C Fitzgerald, Barbara Nutzinger, Aisling M Redmond, Christine Loreno, Sujath Abbas, Adam Freeman, Calvin Cheah, Hannah Coles, Curtis Millington (Early Cancer Institute, University of Cambridge, Cambridge, UK), Paul A W Edwards (Early Cancer Institute, University of Cambridge, Cambridge, UK, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK), Matthew Eldridge, Maria Secrier, Ginny Devonshire, Sriganesh Jammula (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK), Maria O’Donovan, Ahmad Miremadi, Shalini Malhotra, Monika Tripathi (Early Cancer Institute, University of Cambridge, Cambridge, UK, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK), Jim Davies, Charles Crichton (Department of Computer Science, University of Oxford, UK, OX1 3QD), Elizabeth C Smyth, Nick Carroll, Richard H Hardwick, Peter Safranek, Andrew Hindmarsh, Vijayendran Sujendran (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK, CB2 0QQ), Nicola Grehan (Early Cancer Institute, University of Cambridge, Cambridge, UK, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK, CB2 0QQ), Yeng Ang (Salford Royal NHS Foundation Trust, Salford, UK, M6 8HD, Wigan and Leigh NHS Foundation Trust, Wigan, Manchester, UK, WN1 2NN, GI science centre, University of Manchester, UK, M13 9PL), Shaun R Preston, Izhar Bagwan (Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK, GU2 7XX), Vicki Save, Richard J E Skipworth (Edinburgh Royal Infirmary, Edinburgh, UK, EH16 4SA), Philippe Taniere, Sonia Puig, Gianmarco Contino (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, B15 2GW), Ben L Grace (University Hospital Southampton NHS Foundation Trust, Southampton, UK, SO16 6YD), Timothy J Underwood, Robert C Walker (University Hospital Southampton NHS Foundation Trust, Southampton, UK, SO16 6YD, Cancer Sciences Division, University of Southampton, Southampton, UK, SO17 1BJ), Stephen J Hayes(Salford Royal NHS Foundation Trust, Salford, UK, M6 8HD, Faculty of Medical and Human Sciences, University of Manchester, UK, M13 9PL), Ula Mahadeva (Guy’s and St Thomas’s NHS Foundation Trust, London, UK, SE1 7EH), Grant Sanders, Richard Berrisford, David Chan (Plymouth Hospitals NHS Trust, Plymouth, UK, PL6 8DH), Ed Cheong, Bhaskar Kumar, L Sreedharan (Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK, NR4 7UY), Simon L Parsons, Irshad Soomro, Philip Kaye (Nottingham University Hospitals NHS Trust, Nottingham, UK, NG7 2UH), Laurence Lovat, Rehan Haidry(University College London, London, UK, WC1E 6BT), Michael Scott (Wythenshawe Hospital, Manchester, UK, M23 9LT), Ted R. Hupp (Edinburgh University, Edinburgh, UK, EH8 9YL), Vicky Goh, Francesca D Ciccarelli (King’s College London, London, UK, WC2R 2LS), Jesper Lagergren (Guy’s and St Thomas’s NHS Foundation Trust, London, UK, SE1 7EH, Karolinska Institute, Stockholm, Sweden, SE-171 77), Sharmila Sothi (University Hospitals Coventry and Warwickshire NHS, Trust, Coventry, UK, CV2 2DX), Suzy Lishman (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK, Peterborough Hospitals NHS Trust, Peterborough City Hospital, Peterborough, UK, PE3 9GZ), Andrew Beggs (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, B15 2GW, Institute of Cancer and Genomic sciences, University of Birmingham, B15 2TT), Andrew Sharrocks (GI science centre, University of Manchester, UK, M13 9PL.), George B Hanna, Christopher J Peters,Krishna Moorthy (Department of Surgery and Cancer, Imperial College, London, UK, W2 1NY), Anna Grabowska (Queen’s Medical Centre, University of Nottingham, Nottingham, UK), Olga Tucker (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, B15 2GW, Heart of England NHS Foundation Trust, Birmingham, UK, B9 5SS), Richard Turkington, Damian McManus, Helen Coleman (Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Northern Ireland BT7 1NN), Russell D Petty (Tayside Cancer Centre, Ninewells Hospital and Medical School, Dundee, DD1 9SY), Freddie Bartlett (Portsmouth Hospitals NHS Trust, Portsmouth, PO6 3LY), J Robert O’Neill (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK, CB2 0QQ, Edinburgh Royal Infirmary, Edinburgh, UK, EH16 4SA, Edinburgh University, Edinburgh, UK, EH8 9YL), James Gossage, Andrew Davies, Fuju Chang (Guy’s and St Thomas’s NHS Foundation Trust, London, UK, SE1 7EH, King’s College London, London, UK, WC2R 2LS), John Saunders (Salford Royal NHS Foundation Trust, Salford, UK, M6 8HD, Nottingham University Hospitals NHS Trust, Nottingham, UK, NG7 2UH).
Keywords
- Humans
- Barrett Esophagus/diagnosis
- Esophageal Neoplasms/diagnosis
- Metaplasia
- Endoscopy, Gastrointestinal
- Adenocarcinoma
