1. ¹Department of Surgery, Academic Medical Centre at the University of Amsterdam, Amsterdam, The Netherlands
2. ²Department of Medical Oncology, Academic Medical Centre at the University of Amsterdam, Amsterdam, The Netherlands
3. ³Department of Pathology, Academic Medical Centre at the University of Amsterdam, Amsterdam, The Netherlands
4. ⁴Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands

Correspondence: Dr JB Tuynman, Department of Surgery, Academic Medical Centre, PO Box 22660, Meibergdreef 9, Amsterdam 1100DD, The Netherlands. E-mail: J.B.Tuynman@amc.uva.nl

Received 28 August 2007; Revised 7 January 2008; Accepted 15 January 2008.

Abstract

Oesophageal adenocarcinoma is an aggressive malignancy with propensity for early lymphatic and haematogenous dissemination. Since conventional TNM staging does not provide accurate prognostic information, novel molecular prognostic markers and potential therapeutic targets are subject of intense research. The aim of the present study was to study the prognostic significance of Met, the hepatic growth factor (HGF) receptor and a possible target for therapy in comparison to cyclooxygenase-2 (COX-2). Tumour sections from 145 consecutive patients undergoing intentionally curative surgery for oesophageal adenocarcinoma were immunohistochemically analysed for Met and COX-2 expression. Clinicopathological data were prospectively collected for all patients. Patients with high Met expression had significantly reduced overall and disease-specific 5-year survival rates (P0.001 and P0.001, respectively) and were more likely to develop distant metastases (P=0.002) and local recurrences (P=0.004) compared to patients with low Met expression. High COX-2 expression tended to be correlated with poor long-term survival but this did not reach statistical significance. Expression of Met was recognised as a significant and independent prognostic factor by stage-specific analysis and multivariate analysis (relative risk=2.3; 95% CI=1.3–4.1). These findings support the importance of Met in oesophageal adenocarcinoma and support the concept of Met tyrosine kinase inhibition as (neo-) adjuvant treatment.