Oncotarget

Research Papers:

Tenascin-C and fibronectin in normal esophageal mucosa, Barrett’s esophagus, dysplasia and adenocarcinoma

Joni Leppänen, Sara Bogdanoff, Petri P. Lehenkari, Juha Saarnio, Joonas H. Kauppila, Tuomo J. Karttunen, Heikki Huhta and Olli Helminen _

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Oncotarget. 2017; 8:66865-66877. https://doi.org/10.18632/oncotarget.19196

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Abstract

Joni Leppänen1, Sara Bogdanoff1, Petri P. Lehenkari1, Juha Saarnio1, Joonas H. Kauppila1,2, Tuomo J. Karttunen1, Heikki Huhta1,* and Olli Helminen1,*

1Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland

2Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

*Equal contribution as senior author

Correspondence to:

Olli Helminen, email: olli.helminen@oulu.fi

Keywords: esophageal adenocarcinoma, Barrett’s esophagus, tenascin-C, fibronectin, extracellular matrix

Received: January 06, 2017     Accepted: June 19, 2017     Published: July 12, 2017

ABSTRACT

Background: 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.

Results: Stromal 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.

Methods: Tenascin-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.

Conclusions: 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.


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