ERBB2 EXPRESSION IN OESOPHAGEAL ADENOCARCINOMA AND BARRETT’S OESOPHAGUS: DEMONSTRATING THE POTENTIAL FOR A PRE-EMPTIVE STRIKE

摘要: Introduction: The incidence of oesophageal adenocarcinoma (OAC) has increased fourfold in the west 30 years and been highlighted as a major public health concern. It dismal 15% 5-year survival due to its late presentation limited benefit current chemotherapy regimens. Targeted therapies have potential revolutionise shown ErbB2-overexpressing breast tumours, which account for 25% cases. role ErbB family Barrett’s oesophagus OAC development progression remains be fully explored. Aims Methods: timing frequency ErbB2 overexpression was determined using tissue microarrays representing 136 tumours cohort 73 patients with high-grade dysplasia (HGD). Low-grade (LGD) or non-dysplastic intestinal metaplasia biopsies were also available from these 43 53 cases, respectively. amplified cell lines, OE19 OE33, used explore molecular consequences overexpression, confirmed Chinese hamster ovary (CHO) cells transfected and/or epidermal growth factor receptor (EGFR) constructs resection specimens. Results: Nine (7%) had amplification. Six (8%) amplification HGD areas; overall LGD two (5%), one cases present adjacent HGD. No observed without dysplasia. In lines associated constitutive phosphorylation EGFR absence exogenous ligand. Constitutive EGFR-ErbB2 heterodimers demonstrated by immunoprecipitation continuous activation downstream mitogen-activated protein kinase Akt pathways. CHO that low levels resulted phosphorylation. clinical relevance observations seven consecutive specimens both activation. Conclusion: occurs before invasion similar OAC. presence activation, ErbB2-EGFR pathway provides evidence key ErbB-targeted therapies, their toxicity, may play chemoprevention oesophagus.