The Clinicopathological Significance of Epithelial Mesenchymal Transition Associated Protein Expression in Head and Neck Squamous Cell Carcinoma

Abstract

BackgroundEpithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC).MethodsA total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis.ResultsThe E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival.ConclusionsThese findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.

EZH2 overexpression in head and neck cancer is related to lymph node metastasis

“…Our observation is in line with previous immunohistochemistry studies reporting a correlation between EZH2 expression and lymph node metastasis in head and neck cancers . For example, Wang et alshowed a 1.5‐fold increase in EZH2 levels in nodal‐negative as compared to nodal‐positive cancers and Kim et al reported 15% vs 35% EZH2‐positive cancers in subsets of nodal‐negative and nodal‐positive head and neck cancers, respectively. It is believed that EZH2 exerts its oncogenic function through transcriptional deregulation of cancer‐relevant processes including cell differentiation and growth, adhesion, motility, and apoptosis .…”

“…The increasing level of EZH2 expression in patients with higher lymph node metastasis stage suggests a contribution of EZH2 to tumor cell dissemination. In addition, it makes EZH2 an interesting candidate for a clinical biomarker that may aid in decisions on adjuvant treatment in curatively resected HNSCC . Our observation is in line with previous immunohistochemistry studies reporting a correlation between EZH2 expression and lymph node metastasis in head and neck cancers .…”

“…In addition, it makes EZH2 an interesting candidate for a clinical biomarker that may aid in decisions on adjuvant treatment in curatively resected HNSCC . Our observation is in line with previous immunohistochemistry studies reporting a correlation between EZH2 expression and lymph node metastasis in head and neck cancers . For example, Wang et alshowed a 1.5‐fold increase in EZH2 levels in nodal‐negative as compared to nodal‐positive cancers and Kim et al reported 15% vs 35% EZH2‐positive cancers in subsets of nodal‐negative and nodal‐positive head and neck cancers, respectively.…”

“…For example, Chang et al reported 82% EZH2‐positive tumors including 53.3% with high expression in a TMA of 120 head and neck cancers. Zhou et al found 50% EZH2‐positive cancers in 97 HNSCC, and Zheng et al reported EZH2 overexpression in 97% of 30 oral tongue carcinomas, while Kim et al found increased expression of EZH2 in 24% of 118 HNSCC TMAs. In normal tissue, EZH2 staining was either observed in basal layers or staining was completely lacking.…”

“…Consequently, anti‐EZH2 therapies are currently under development . Recent studies on 30‐120 head and neck cancers also reported that EZH2 overexpression may be linked to adverse features of this disease and may represent a potent predictor of patient survival …”