N-cadherin expression is correlated with metastasis of spindle cell carcinoma of head and neck region

Abstract

Spindle cell carcinoma (SpCC) is a biphasic tumor composed of conventional squamous cell carcinoma and a malignant spindle cell component. SpCC expresses both epithelial and mesenchymal markers by immunohistochemical analysis. There is mounting evidence for sarcomatoid transformation from the epithelial component, supporting the theory that SpCC is a monoclonal neoplasm originating from a stem cell giving rise to both components. The loss of E-cadherin and the gain of N-cadherin expression are known as the "cadherin switching". Cadherin switching is a major hallmark of epithelial-mesenchymal transition (EMT). EMT is a crucial process in cancer progression providing cancer cells with the ability to escape from the primary focus, to invade stromal tissues, and to migrate to distant regions. Although E-cadherin down-regulation is well known in various cancers, there are a few studies on N-cadherin expression in cancer. Here, therefore, we investigated N-cadherin expression in the progression of head and neck SpCC. First, we examined cadherin switching in our established SpCC cell lines, SpCC-1 and SpCC-2. SpCC-1 and SpCC-2 cells were spindle in shape and showed cadherin switching. Moreover, we examined N-cadherin expression in 15 SpCC cases by immunohistochemistry. Although N-cadherin expression was not observed in non-neoplastic squamous epithelium, high expression of N-cadherin was observed in 10 of 15 SpCC cases. Interestingly, 6 of 7 SpCC cases with metastasis showed high expression of N-cadherin. In conclusion, our findings suggest that N-cadherin may play an important role in metastasis of SpCC in addition to the pathogenesis of SpCC of the head and neck.