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      Study of β-catenin, E-cadherin and vimentin in oral squamous cell carcinoma with and without lymph node metastases

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          Abstract

          Abstract
          Background

          Despite great improvement in the surgical treatment and adjunctive therapy for oral squamous cell carcinoma (OSCC), prognosis remains dismal in advanced cases. Regional metastatic disease is known to reduce recurrence free survival and disease specific survival significantly. The present study was conducted to evaluate the role of cell adhesion molecules β-catenin, E-cadherin and vimentin in predicting tumour metastasis of OSCC.

          Methods

          A total of sixty cases of oral squamous cell carcinoma were included for the study which comprised of 30 cases with lymph node metastases and 30 cases without metastases. Immunohistochemistry was performed for β-catenin, E-cadherin and vimentin on both the test groups along with 30 controls from normal buccal mucosa and inflammatory lesions each.

          Results

          There was no significant difference between the immunoreactivity for β-catenin, E-cadherin and vimentin between OSCC with and without lymph node metastases. Vimentin immunopositivity was noted with varying intensity in all cases of OSCC.

          Conclusions

          E-cadherin and β-catenin are probably not the key determinants for regional metastases in OSCC. The role of vimentin expression in OSCC and metastases is controversial and needs to be studied further.

          Virtual slides

          The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6506095201182002.

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          Most cited references40

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          Global cancer statistics

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            Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts

            Rat 3Y1 cells acquire metastatic potential when transformed with v-src, and this potential is enhanced by double transformation with v-src and v-fos (Taniguchi, S., T. Kawano, T. Mitsudomi, G. Kimura, and T. Baba. 1986. Jpn. J. Cancer Res. 77:1193-1197). We compared the activity of cadherin cell adhesion molecules of normal 3Y1 cells with that of v-src transformed (SR3Y1) and v-src and v-fos double transformed (fosSR3Y1) 3Y1 cells. These cells expressed similar amounts of P-cadherin, and showed similar rates of cadherin-mediated aggregation under suspended conditions. However, the aggregates or colonies of these cells were morphologically distinct. Normal 3Y1 cells formed compacted aggregates in which cells are firmly connected with each other, whereas the transformed cells were more loosely associated, and could freely migrate out of the colonies. Overexpression of exogenous E-cadherin in these transformed cells had no significant effect on their adhesive properties. We then found that herbimycin A, a tyrosine kinase inhibitor, induced tighter cell-cell associations in the aggregates of the transformed cells. In contrast, vanadate, a tyrosine phosphatase inhibitor, inhibited the cadherin-mediated aggregation of SR3Y1 and fosSR3Y1 cells but had little effect on that of normal 3Y1 cells. These results suggest that v-src-mediated tyrosine phosphorylation perturbs cadherin function directly or indirectly, and the inhibition of tyrosine phosphorylation restores cadherin action to the normal state. We next studied tyrosine phosphorylation on cadherins and the cadherin- associated proteins, catenins. While similar amounts of catenins were expressed in all of these cells, the 98-kD catenin was strongly tyrosine phosphorylated only in SR3Y1 and fosSR3Y1 cells. Cadherins were also weakly tyrosine phosphorylated only in the transformed cells. The tyrosine phosphorylation of these proteins was enhanced by vanadate, and inhibited by herbimycin A. Thus, the tyrosine phosphorylation of the cadherin-catenin system itself might affect its function, causing instable cell-cell adhesion.
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              Snail-dependent and -independent epithelial-mesenchymal transition in oral squamous carcinoma cells.

              Disappearance of E-cadherin is a milestone for epithelial-mesenchymal transition (EMT), found both in carcinomas and in some fibrotic diseases. We have studied the mechanisms of EMT in oral squamous cell carcinoma (SCC) cells isolated from primary tumor (43A) and its recurrent tumor (43B). Whereas the cells from primary carcinoma displayed a typical phenotype of squamous epithelial cells including E-cadherin and laminin-332 (laminin-5), cells from recurrent tumor expressed characteristics of dedifferentiated, EMT-experienced tumors. 43B cells expressed E-cadherin repressors ZEB-1/deltaEF1 and especially ZEB-2/SIP1, which therefore appear as candidates for endogenous EMT in these cells. Differences between endogenous and exogenous EMT were assessed by transfecting 43A cells with SNAIL cDNA. SNAIL-transfected cells showed complete EMT phenotype with fibroblastoid appearance, vimentin filaments, E-cadherin/N-cadherin switch, lack of hemidesmosomes and, as a new feature of EMT, lack of laminin-332 synthesis. Upregulation of ZEB-1 and ZEB-2 was evident in these cells, suggesting that SNAIL can regulate these E-cadherin repressors. New monoclonal antibodies against SNAIL showed nuclear immunoreactivity not only in the SNAIL-transfected cells but also in carcinoma cells lacking production of Lm-332 and showing signs of EMT. These results suggest that changes in the epithelial cell differentiation program and EMT in SCC cells can result from the interplay among several E-cadherin repressors; however, SNAIL alone is able to accomplish a complete EMT.
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                Author and article information

                Contributors
                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central
                1746-1596
                2014
                21 July 2014
                : 9
                : 145
                Affiliations
                [1 ]Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
                [2 ]Department of Otorhinolaryngology and Head & Neck Surgery, All India Institute of Medical Sciences, New Delhi, India
                Article
                1746-1596-9-145
                10.1186/1746-1596-9-145
                4223686
                25047112
                493ed0fa-ee96-4a26-8499-86c08899361c
                Copyright © 2014 Balasundaram et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 January 2014
                : 9 February 2014
                Categories
                Research

                Pathology
                squamous cell carcinoma,metastases,lymph node,β-catenin,vimentin,e-cadherin
                Pathology
                squamous cell carcinoma, metastases, lymph node, β-catenin, vimentin, e-cadherin

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