Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

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 (Pp0.001 and Pp0.001, respectively) and were more likely to develop distant metastases (P ¼ 0.002) and local recurrences (P ¼ 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 ¼ 2.3; 95% CI ¼ 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.

EGFR family and cMet expression profiles and prognostic significance in esophagogastric adenocarcinoma

“…Clinically, co-amplification of cMet with HER2 was associated with poor prognosis and treatment resistance (41). Tuynman and colleagues showed that cMet expression was found in 54% of EGA which was associated with a significantly shorter 5-year disease specific and OS with an increased likelihood to develop both local recurrences and distant metastases (42). Similarly, Lennerz et al demonstrated that EGA tumors harboring cMet overexpression were associated with highgrade histology, advanced stages and had shorter OS (7.1 vs. 16.2 months) (43).…”

Safety, Pharmacokinetics, and Pharmacodynamics of AMG 102, a Fully Human Hepatocyte Growth Factor–Neutralizing Monoclonal Antibody, in a First-in-Human Study of Patients with Advanced Solid Tumors

“…In addition, c-Met was expressed in the majority of available patient tumor samples. Although both HGF/SF and c-Met are well-documented prognostic markers of disease progression and survival (34)(35)(36)(37)(38)(39)(40), additional studies are required to determine whether these markers will be useful for predicting the efficacy of HGF/SF-c-Met axis-targeted therapies.…”

Expression of receptor tyrosine kinases in esophageal carcinosarcoma

“…Previous studies have reported overexpression of MET in up to 54% of esophageal adenocarcinomas (EAs) (21) and 92% of ESCCs (22), and expression levels are thought to correlate with tumor development, progression, and prognosis in patients with EA and ESCC (21)(22)(23) EGFR overexpression has been reported in 33-50% of ESCCs (24,25) and 55% of EAs (26). Amplification of the EGFR gene has also been reported in ~30% of ESCCs and 6-11% of EA cases (25,27).…”