Expression and Role of E-Cadherin, β-Catenin, and Vimentin in Human Papillomavirus–Positive and Human Papillomavirus–Negative Oropharyngeal Squamous Cell Carcinoma

Abstract

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, β-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 β-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, β-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 β-catenin and vimentin pathways in carcinogenic process. More, β-catenin may serve as a marker for the occurrence of regional metastasis:

Induction of apoptosis using ATN as a novel Yes‐associated protein inhibitor in human oral squamous cell carcinoma cells

“…E-cadherin is not only an epithelial marker during the occurrence of EMT, but also a regulator of YAP in controlling cancer cell proliferation, 55 while vimentin is a protein normally expressed in mesenchymal cells and serves as a canonical marker of EMT. 56 Notably, strong stromal vimentin expression was observed in 54% of human papillomavirus-positive OSCC clinical samples indicating the important role of vimentin in carcinogenesis. 56 The Bcl-2 family regulates apoptosis and holds great promise for cancer treatment.…”

“…The results of the present study showed that ATN decreased the levels of vimentin and YAP, accompanied by increased levels of E‐cadherin in SCC2095 cells. E‐cadherin is not only an epithelial marker during the occurrence of EMT, but also a regulator of YAP in controlling cancer cell proliferation, 55 while vimentin is a protein normally expressed in mesenchymal cells and serves as a canonical marker of EMT 56 . Notably, strong stromal vimentin expression was observed in 54% of human papillomavirus‐positive OSCC clinical samples indicating the important role of vimentin in carcinogenesis 56 …”

Biomarker Potential of Vimentin in Oral Cancers

“…In addition, cell membrane β-catenin expression was significantly associated with vimentin in HPV-associated oropharyngeal squamous cell carcinoma [63]. In an OSCCderived cell line Tca8113, treatment of exogenous TGFβ1 upregulated vimentin expression at both mRNA and protein levels.…”

Viruses in colorectal cancer

“…In addition, more and more experimental evidence links HPV infection to a pro‐oncogenic modulation of the Wnt/β‐catenin pathway [ 147 ]. For example, in oropharyngeal cancer, tumour cells infected with HPV expressed higher β‐catenin than HPV‐negative tumours [ 148 ]. Furthermore, the nuclear localization of β‐catenin was higher in HPV‐positive tumours than HPV‐negative control tumours [ 149 ], a characteristic also confirmed in tonsillar tumours [ 150 ].…”