Abstract
BackgroundTenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages.ResultsStromal tenascin-C and fibronectin expression were found in all evaluated lesion types. Expression of both molecules increased from gastric metaplasia towards adenocarcinoma (p<0.05). In carcinomas, tenascin-C expression in the bulk was associated with T-stage (p=0.006), presence of lymph node (p=0.004) and distant organ metastases (p=0.007). Abundant tenascin-C expression associated with poor survival (p=0.034) in univariate analysis. Fibronectin expression associated to T-stage (p=0.030). Expression of tenascin-C or fibronectin in the tumor invasive front was not associated to clinicopathological variables or survival. No significant correlation with tumor/stroma percentage, cancer-associated fibroblasts or mean vascular density was observed with either tenascin-C or fibronectin.MethodsTenascin-C and fibronectin were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal adenocarcinoma (n=90) or dysplasia (n=30). Structures and lesion were evaluated including normal esophagus (n=77), gastric (n=61) or intestinal (n=51) metaplasia without dysplasia, and low-grade (n=42) or high-grade (n=34) dysplasia, and esophageal adenocarcinoma (n=90). In carcinomas, both bulk and invasive front were separately evaluated. In addition, tumor/stroma percentage, cancer-associated fibroblasts and mean vascular density were evaluated.ConclusionsTenascin-C and fibronectin are upregulated in esophageal adenocarcinoma when compared to Barrett’s esophagus and dysplasia. Increased tenascin-C expression is associated with metastasis and poor prognosis in esophageal adenocarcinoma.
Highlights
The incidence of esophageal adenocarcinoma has been increasing rapidly in the Western World during the last decades
Tenascin-C and fibronectin are upregulated in esophageal adenocarcinoma when compared to Barrett’s esophagus and dysplasia
Increased tenascin-C expression is associated with metastasis and poor prognosis in esophageal adenocarcinoma
Summary
The incidence of esophageal adenocarcinoma has been increasing rapidly in the Western World during the last decades. Tenascins are a family of large adhesive of glycoproteins of the extracellular matrix that affect tissue elasticity and architecture and cellular responses [2]. Increased expression of tenascin-C has been detected in several types of benign and malignant neoplasms, and is found to associate to the invasive and metastatic potential of malignant tumors, for example esophageal squamous cell carcinoma and colorectal cancer [3, 4]. A single study has reported no expression of tenascin-C in 6 patients with Barrett’s esophagus and upregulation of tenascin-C in 15 patients with esophageal adenocarcinoma, showing association to poor tumor differentiation [5]. Tenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages
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