Overexpression of CMET is associated with signal transducer and activator of transcription 3 activation and diminished prognosis in oesophageal adenocarcinoma but not in squamous cell carcinoma

Abstract

Background: Inhibition of cMet is a promising therapeutic approach in human cancer, but few data in oesophageal cancer exist.

Methods: Expression of mesenchymal-epithelial transition factor (cMet), epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) were investigated immunohistochemically in 246 oesophageal carcinomas (128 adenocarcinomas (AC); 118 squamous cell carcinomas (SCC)) and corresponding metastases in a subset of AC (n=42). Data on phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and HER2 expression and on lymphovascular invasion (LVI) of tumour cells were available from previous studies.

Results: Overexpression of cMet was seen in 44 (34.4%) of AC, and nine (7.6%) of SCC (p<0.001, Chi square test). In AC but not in SCC, cMet expression correlated with EGFR expression (p<0.001, Chi square test), pSTAT3 expression (p=0.01, Chi square tests) and LVI of tumour cells (p<0.001, Chi square test). Overexpression of cMet was associated with shorter disease free, disease specific and overall survival of AC patients (p<0.05, Cox regression, respectively). All cMet positive ACs in which metastases were investigated had also cMet positive lymph node and distant metastases, but 25% of cMet negative primary tumours showed cMet positive lymph node and 33% distant metastases.

Conclusions: CMet plays no relevant role in most oesophageal SCC. In contrast, cMet overexpression seems to be a key oncogene in about 35% of oesophageal AC, representing a highly promising therapeutic target and prognostic factor.

Keywords: C-Met; MET; Oesophageal cancer; Prognosis; Survival; cMet.