Upper GI 01

• Published in: British journal of surgery Vol. 89; no. S1; p. 42
• Main Authors: O'Riordan, J.M.W., Abdel-Latif, M., McNamara, D., Ravi, N., Kelleher, D., Keeling, P.W.N., Reynolds, J.V.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 2002
• ISSN: 0007-1323; 1365-2168
• DOI: 10.1046/j.1365-2168.89.s.1.27_1.x

Aims: A molecular understanding of Barrett's tumourigenesis may impact on treatment, tumour prevention and surveillance policies. Nuclear factor‐κB regulates several cellular genes that participate in the inflammatory and immune responses, and this study examined NF‐κB in the spectrum of Barrett's disease. Methods: Fifty‐one patients were studied, 26 with Barrett's oesophagus and 35 with Barrett's associated adenocarcinoma. Electromobility shift assay measured NF‐κB expression in nuclear extracts of fresh tissue tumour samples and Barrett's biopsies. Only patients with macroscopic evidence of Barrett's greater than 3 cm were included. All Barrett's patients had samples of non‐Barrett's oesophagus analysed as controls and completed a detailed reflux questionnaire. Correlation was also made with DeMeester scores. Results: Increased NF‐κB activity was observed in 16/26 (61.5 per cent) patients in Barrett's epithelium compared with samples of squamous epithelium above the Barrett's segment. All Barrett's patients with dysplasia (N = 5) showed significantly increased NF‐κB expression. The expression of NF‐κB did not correlate with symptomatology, length of Barrett's, DeMeester scores or use of proton pump inhibitors. Twenty‐eight of 35 (80 per cent) patients with oesophageal adenocarcinoma showed highly elevated NF‐κB expression, and this correlated with late stage of disease in these patients. NF‐κB was significantly decreased in response to neoadjuvant chemotherapy and radiation therapy. Conclusions: These data show for the first time that patients with Barrett's oesophagus have progressive increase of NF‐κB expression from metaplasia through dysplasia and adenocarcinoma. NF‐κB is a central regulator of inflammation and tumourigenesis, and further understanding of factors regulating NF‐κB activation may offer prospects for novel anti‐inflammatory and antitumour therapies in patients with Barrett's oesophagus.