The role of biological markers of epithelial to mesenchymal transition in oesophageal adenocarcinoma, an immunohistochemical study

Abstract

Background: E-cadherin, β-catenin, epidermal growth factor receptor (EGFR), neuronal cadherin (N-cadherin) and Cyclin D1 are involved in epithelial to mesenchymal transition (EMT). However, the prognostic significance of EMT markers in oesophageal adenocarcinoma (OAC) is unknown. Aim of this study was to evaluate the prognostic value of, and the association between different EMT markers in OAC.

Methods: Tumour cores of 154 patients with OAC were included in a tissue microarray. Scoring criteria was based on immunohistochemical staining intensity.

Results: EMT-associated markers were expressed in OAC: reduced membranous E-cadherin and β-catenin were seen in 11.4% and 51.7%, nuclear β-catenin in 19.1% and EGFR and Cyclin D1 overexpression in 56.5% and 27.4% of tumours. Mesenchymal marker N-cadherin was not expressed in OAC. A positive correlation was seen between membranous β-catenin and E-cadherin expression (R=0.209, p=0.001) and between EGFR and Cyclin D1 (R=0.257, p=0.002). In univariate analysis, EGFR overexpression and membranous β-catenin staining were significantly associated with a poor survival (HR 2.145; 95% CI 1.429 to 3.218, p<0.001 and HR 1.665; 95% CI 1.114 to 2.488; p=0.013). However, Cyclin D1 (HR 1.092; 95% CI 0.702 to 1.698; p=0.697), nuclear β-catenin (HR 1.322; 95% CI 0.799 to 2.189; p=0.277) and E-cadherin (HR 1.012; 95% CI 0.554 to 1.851; p=0.968) were not associated with survival. In multivariate analysis, EGFR overexpression was an independent prognostic factor for poor survival (HR 1.678; 95% CI 1.055 to 2.668; p=0.029) together with T stage (HR 2.759; 95% CI 1.356 to 5.576; p=0.005).

Conclusions: This study supports the presence of EMT in OAC. Moreover, EGFR overexpression was independently associated with a poor survival.

Keywords: ADHESION; CANCER; GASTROINTESTINAL DISEASE; GI NEOPLASMS; IMMUNOHISTOCHEMISTRY.