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Open AccessArticle

Slug Is A Surrogate Marker of Epithelial to Mesenchymal Transition (EMT) in Head and Neck Cancer

1
Department for Otorhinolaryngology, Head and Neck surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
2
Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria
3
Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck; 6020 Innsbruck, Austria
4
Tyrolean Cancer Research Institute, 6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(7), 2061; https://doi.org/10.3390/jcm9072061
Received: 23 May 2020 / Revised: 22 June 2020 / Accepted: 23 June 2020 / Published: 30 June 2020
Background: Epithelial to mesenchymal transition (EMT) promotes therapy resistance in head and neck cancer (HNC) cells. In this study, EMT was quantified in HNC tumor samples by the cellular co-localization of cytokeratin/vimentin, E-cadherin/β-catenin and by Slug expression. Methods: Tissue samples from HNC patients were stained with antibody pairs against cytokeratin/vimentin and E-cadherin/β-catenin. Epithelial–mesenchymal co-localization was quantified using immunofluorescence multichannel image cytometry. Double positivity was confirmed using confocal microscopy. Slug was semi-quantified by 2 specialists and quantified by bright field image cytometry. Results: Tumor samples of 102 patients were investigated. A loss of E-cadherin positive cells (56.9 ± 2.6% vs. 97.9 ± 1.0%; p < 0.0001) and E-cadherin/β-catenin double positive cells (15.4 ± 5.7% vs. 85.4 ± 1.2%; p < 0.0001) was observed in tumor samples. The percentage of Slug positive cells was increased in tumor samples (12.1 ± 3.6% vs. 3.2 ± 2.6%; p = 0.001). Ordinal Slug scores judged by two specialists closely correlated with percentage of Slug-positive cells (Spearman’s rho = 0.81; p < 0.001). Slug score correlated negatively with the percentage of E-cadherin positive cells (r = 0.4; p = 0.006), the percentage of E-cadherin/β-catenin positive cells (r = 0.5; p = 0.001) and positively with cytokeratin/vimentin positive cells (r = 0.4, p = 0.003). Conclusion: EMT can be assessed in HNC tumor probes by cytokeratin/vimentin co-expression and loss of E-cadherin/β-catenin co-expression. Slug score provides a convenient surrogate marker for EMT. View Full-Text
Keywords: image cytometry; p16; p53; cancer stem cells; E-cadherin; β-catenin; EMT; head and neck cancer image cytometry; p16; p53; cancer stem cells; E-cadherin; β-catenin; EMT; head and neck cancer
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Steinbichler, T.B.; Dudas, J.; Ingruber, J.; Glueckert, R.; Sprung, S.; Fleischer, F.; Cidlinsky, N.; Dejaco, D.; Kofler, B.; Giotakis, A.I.; Skvortsova, I.I.; Riechelmann, H. Slug Is A Surrogate Marker of Epithelial to Mesenchymal Transition (EMT) in Head and Neck Cancer. J. Clin. Med. 2020, 9, 2061.

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