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      Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity

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          Abstract

          Background

          Intermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCC's) of the oral cavity.

          Methods

          308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Ck's), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis.

          Results

          The expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCC's and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin.

          Conclusion

          The expression of Ck 8/18 in SCC's of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCC's.

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          Most cited references34

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          Tissue microarrays for high-throughput molecular profiling of tumor specimens.

          Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.
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            The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells.

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              Keratin expression in human tissues and neoplasms.

              Keratin expression in human tissues and neoplasms Keratin filaments constitute type I and type II intermediate filaments (IFs), with at least 20 subtypes named keratin 1-20. Since certain keratin subtypes are only expressed in some normal human tissues but not others, and vice versa, various tissues have been subclassified according to the pattern of keratin staining. Simple epithelia generally express the simple epithelial keratins 7, 18, 19, and 20, while complex epithelia express complex epithelial keratins 5/6, 10, 14, and 15. When an epithelium undergoes malignant transformation, its keratin profile usually remains constant. The constitution and expression patterns of keratin filaments in human epithelial neoplasms are complex and often distinctive. In this article, we first briefly review the molecular and cell biology of keratin filaments. We then focus on the expression patterns of keratin filaments in various human neoplasms.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                2006
                13 January 2006
                : 6
                : 10
                Affiliations
                [1 ]Department of Cranio-Maxillofacial Surgery, University of Muenster, Waldeyerstrasse 30, 48129 Muenster, Germany
                [2 ]Department of Oral and Maxillofacial Surgery, Central German Armed Forces Hospital, Rübenacher Str. 170, 56072 Koblenz, Germany
                [3 ]Institute of Pathology, Klinikum Osnabrueck, Germany
                [4 ]Institute of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20146 Hamburg, Germany
                [5 ]Department of Maxillofacial Surgery, Katharinenhospital Stuttgart, Kriegsbergstrasse 60, 70174 Stuttgart, Germany
                [6 ]Institute of Pathology, University of Muenster, Domagkstraβe 17, 48149 Muenster, Germany
                Article
                1471-2407-6-10
                10.1186/1471-2407-6-10
                1379654
                16412231
                b7d5de00-284d-41ff-a537-a267cd72d71f
                Copyright © 2006 Fillies 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 cited.

                History
                : 11 May 2005
                : 13 January 2006
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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