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      Tenascin-C and fibronectin expression divide early stage tongue cancer into low- and high-risk groups

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          Abstract

          Background:

          Oral tongue squamous cell carcinoma (OTSCC) metastasises early, especially to regional lymph nodes. There is an ongoing debate on which early stage (T1-T2N0) patients should be treated with elective neck dissection. We need prognosticators for early stage tongue cancer.

          Methods:

          Mice immunisation with human mesenchymal stromal cells resulted in production of antibodies against tenascin-C (TNC) and fibronectin (FN), which were used to stain 178 (98 early stage), oral tongue squamous cell carcinoma samples. Tenascin-C and FN expression in the stroma (negative, moderate or abundant) and tumour cells (negative or positive) were assessed. Similar staining was obtained using corresponding commercial antibodies.

          Results:

          Expression of TNC and FN in the stroma, but not in the tumour cells, proved to be excellent prognosticators both in all stages and in early stage cases. Among early stages, when stromal TNC was negative, the 5-year survival rate was 88%. Correspondingly, when FN was negative, no cancer deaths were observed. Five-year survival rates for abundant expression of TNC and FN were 43% and 25%, respectively.

          Conclusions:

          Stromal TNC and, especially, FN expressions differentiate patients into low- and high-risk groups. Surgery alone of early stage primary tumours might be adequate when stromal FN is negative. Aggressive treatments should be considered when both TNC and FN are abundant.

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          Most cited references40

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          Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer.

          Whether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate.
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            Fibronectin fibrillogenesis, a cell-mediated matrix assembly process.

            The extracellular matrix provides a framework for cell adhesion, supports cell movement, and serves to compartmentalize tissues into functional units. Fibronectin is a core component of many extracellular matrices where it regulates a variety of cell activities through direct interactions with cell surface integrin receptors. Fibronectin is synthesized by many adherent cells which then assemble it into a fibrillar network. The assembly process is integrin-dependent and fibronectin-integrin interactions initiate a step-wise process involving conformational activation of fibronectin outside and organization of the actin cytoskeleton inside. During assembly, fibronectin undergoes conformational changes that expose fibronectin-binding sites and promote intermolecular interactions needed for fibril formation. In this review, the main steps of fibronectin assembly are described and recent studies on fibronectin conformational changes are discussed.
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              The role of tenascin-C in tissue injury and tumorigenesis

              The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                28 February 2017
                17 January 2017
                : 116
                : 5
                : 640-648
                Affiliations
                [1 ]Cancer and Translational Medicine Research Unit, University of Oulu , Oulu FI-90014, Finland
                [2 ]Medical Research Centre, Oulu University Hospital , Oulu FI-90014, Finland
                [3 ]Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Karolinska University Hospital , Stockholm 17176, Sweden
                [4 ]Department of Physiology, Institute of Biomedicine, University of Oulu , Oulu FI-90014, Finland
                [5 ]Department of Biochemistry and Molecular Medicine, University of Oulu and Biocenter Oulu , Oulu FI-90014, Finland
                [6 ]Department of Otorhinolaryngology—Head and Neck Surgery, University of Helsinki and Helsinki University Hospital , Helsinki FI-00014, Finland
                [7 ]Department of Research and Development, Finnish Red Cross Blood Service , Helsinki FI-00014, Finland
                [8 ]Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu , Oulu FI-90014, Finland
                [9 ]Northern Laboratory Centre NordLab , Oulu FI-90220, Finland
                [10 ]Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland , Kuopio FI-70211, Finland
                [11 ]Cancer Centre of Eastern Finland and Kuopio University Hospital , Kuopio FI-70210, Finland
                [12 ]Department of Clinical Pathology, Imaging Centre, Kuopio University Hospital , Kuopio FI-70211, Finland
                [13 ]Oral Pathology and Oral Medicine, Dentistry School, Western Paraná State University , Cascavel 85819-110, Brazil
                [14 ]Department of Oral Diagnosis, Oral Pathology Division, Piracicaba Dental School, University of Campinas , Campinas 13414-903, Brazil
                [15 ]Medical Informatics and Statistics Research Group, University of Oulu , Oulu FI-90014, Finland
                [16 ]Department of Oral and Maxillofacial Diseases, University of Helsinki , Helsinki FI-00014, Finland
                Author notes
                Article
                bjc2016455
                10.1038/bjc.2016.455
                5344290
                28095396
                7cb1f8aa-7602-44b4-93b3-76e126441b19
                Copyright © 2017 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 12 September 2016
                : 18 November 2016
                : 20 December 2016
                Categories
                Molecular Diagnostics

                Oncology & Radiotherapy
                tongue cancer,prognosis,mesenchymal stromal cell,tenascin-c,fibronectin,stroma,immunohistochemistry,tumour microenvironment

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