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Oropharyngeal squamous cell carcinoma (OPSCC) is subclassified by the World Health Organization into two different entities: human papillomavirus (HPV)-positive and HPV-negative tumors. HPV infection promotes the epithelial-to-mesenchymal transition (EMT) and transformation of keratinocyte stem cells into cancer stem cells. EMT is a crucial process in the carcinogenesis of epithelial-derived malignancies, and we aimed to study the role of its markers in OPSCC. This study consists of 202 consecutive OPSCC patients diagnosed and treated with curative intent. We examined E-cadherin, beta-catenin, and vimentin expression using immunohistochemistry and compared these with tumor and patient characteristics and treatment outcome. We found that the cell-membranous expression of beta-catenin was stronger in HPV-positive than in HPV-negative tumors, and it was stronger in the presence of regional metastasis. The stromal vimentin expression was stronger among HPV-positive tumors. A high E-cadherin expression was associated with tumor grade. No relationship between these markers and survival emerged. In conclusion, beta-catenin and vimentin seem to play different roles in OPSCC: the former in the tumor tissue itself, and the latter in the tumor stroma. HPV infection may exploit the beta-catenin and vimentin pathways in carcinogenic process. More, beta-catenin may serve as a marker for the occurrence of regional metastasis

Context: Anaplastic thyroid cancer cells are characterized by a mesenchymal phenotype, as revealed by spindle-shaped cells and absent or reduced levels of E-cadherin. Epigenetic silencing is considered one of the leading mechanisms of E-cadherin impairment, which causes the acquisition of the invasive and metastatic phenotype of anaplastic thyroid cancer. Objectives: In this studyweinvestigated the effects of histone deacetylase inhibition on E-cadherin expression, cell motility, and invasion in anaplastic thyroid cancer cell cultures. Design: Three stabilized cell lines and primary cultures of anaplastic thyroid cancer were treated with various histone deacetylase inhibitors. After treatment, we evaluated histone acetylation by Western blotting and E-cadherin expression by RT-real time PCR. The proper localization of E-cadherin/β- catenin complex was assessed by immunofluorescence and Western blot. Transcription activity of β-catenin was measured by luciferase reporter gene and cyclin D1 expression. The effect on cell motility and invasion was studied both in vitro using scratch-wound and transwell invasion assays and in anaplastic thyroid carcinomas tumor xenografts in mice in vivo. Results: Histone deacetylase inhibition induced the E-cadherin expression and the proper membrane localization of the E-cadherin/β-catenin complex, leading to reduced cancer cell migration and invasion. Conclusions: We here demonstrate an additional molecular mechanism for the anticancer effect of histone deacetylase inhibition. The antiinvasive effect in addition to the cytotoxic activity of histone deacetylase inhibitors opens up therapeutic perspectives for the anaplastic thyroid tumor that does not respond to conventional therapy.

Epithelial cadherin (E-cadherin, E-cad) is a calcium-dependent cell-cell adhesion molecule that binds cells through homotypic fashion interactions. Its role is crucial in the induction and maintenance of cell polarity and differentiation. Downregulation or loss of its function is associated with an invasive and aggressive phenotype in many types of human cancers. 45 male patients (mean age 63 years, age range from 29 years to 87 years) with transitional cell carcinoma (TCC) of the bladder were included in the study. E-cad expression was estimated immunohistochemically in a semiquantitative fashion using light microscopy. An avidin-biotin immunoperoxidase technique was employed using anti E-cad murine monoclonal antibodies. Loss of the E-cad normal surface expression by the bladder cells was found in 32/45 (71%) of patients compared to normal bladder epithelia observed at the intercellular borders (p