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

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 &lt; 0.0001) and E-cadherin/β-catenin double positive cells (15.4 ± 5.7% vs. 85.4 ± 1.2%; p &lt; 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 &lt; 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.</jats:p

HPV-Induced Oropharyngeal Cancer and the Role of the E7 Oncoprotein Detection via Brush Test

Background: High risk human papillomavirus (hr-HPV)-associated oropharyngeal cancers (OPCs) are characterized by significantly better therapy responses. In order to implement a de-escalated treatment strategy for this tumor entity, it is highly crucial to accurately distinguish HPV-associated OPCs from non-HPV-associated ones. Methods: In this prospective study, 56 patients with histologically confirmed OPC were evaluated. A commercially available sandwich ELISA test system was used for the detection of hr-HPV E7 oncoprotein targeting the genotypes 16, 18 and 45. Results were presented as optical density. Positivity for HPV DNA and p16 immunohistochemistry (IHC) was taken as the reference method. Results: E7 positivity was significantly associated with the reference method (p = 0.048). The sensitivity, specificity, positive predictive value and negative predictive value for the E7 oncoptotein was 60.9% (95% CI 38.5 to 80.3%), 66.7% (95% CI 46% to 83.5%), 64.2% (95% CI 49.4 to 77.4%) and 63.01% (95% CI 48.9–75.2%), respectively, for the cutoff provided by the manufacturer. Conclusions: We found a significant association between E7 oncoprotein detection and the currently used combination. We believe that the use of the ELISA based E7 antigen test could be a valuable addition in cases of ambiguous findings and may be used in combination with other techniques to distinguish between HPV-driven and non-HPV-driven OPCs. However, the low sensitivity of the assay coupled with the small sample size in our study may represent a limitation. We recommend that future larger studies elucidate the diagnostic value of the E7 brush test.</jats:p

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

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/&beta;-catenin and by Slug expression. Methods: Tissue samples from HNC patients were stained with antibody pairs against cytokeratin/vimentin and E-cadherin/&beta;-catenin. Epithelial&ndash;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 &plusmn; 2.6% vs. 97.9 &plusmn; 1.0%; p &lt; 0.0001) and E-cadherin/&beta;-catenin double positive cells (15.4 &plusmn; 5.7% vs. 85.4 &plusmn; 1.2%; p &lt; 0.0001) was observed in tumor samples. The percentage of Slug positive cells was increased in tumor samples (12.1 &plusmn; 3.6% vs. 3.2 &plusmn; 2.6%; p = 0.001). Ordinal Slug scores judged by two specialists closely correlated with percentage of Slug-positive cells (Spearman&rsquo;s rho = 0.81; p &lt; 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/&beta;-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/&beta;-catenin co-expression. Slug score provides a convenient surrogate marker for EMT