Upper GI 01

Abstract

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.