Abstract
The cancer microenvironment (CME) promotes malignant progression of cancer cells by stimulating cell growth, migration and invasion. Cancer-associated fibroblasts (CAFs), prominent features of the CME, interact directly with cancer cells and facilitate epithelial-mesenchymal transition (EMT). The present study examined the spatial distribution of CAFs and EMT on cancer cells in patients with early-stage tongue squamous cell carcinoma (TSCC) and their association with local recurrence. The present study included 14 patients with early-stage TSCC who had undergone glossectomy between 2006 and 2015, of which 7 experienced local recurrence (LR group) and 7 did not (control group). Multiple immunofluorescent analysis (MIA) of PCNA, αSMA, vimentin, E-cadherin and cytokeratin 14 (CK14) was performed on slides obtained from surgical specimens to identify the expression of various cell-specific markers. The number of CAFs in the CME was significantly increased in the LR group (P=0.001). Furthermore, the neighbouring cancer cells were positive for vimentin expression, indicating EMT. However, the present study also identified concurrent expression of CK14 in all vimentin-positive cancer cells, whilst epithelial markers, including E-cadherin, were expressed in certain vimentin-positive cancer cells. Concurrent expression of CK14 and vimentin is not defined as EMT or partial EMT. Therefore, the present study proposed a novel mechanism of anaplastic transition (APT), in which epithelial cancer cells concurrently develop mesenchymal features, which is achieved by pathways other than EMT. APT is characterized such that epithelial cancer cells differentiate into more primitive states, which is different from EMT or partial EMT, and it may be associated with LR. The concept aids in improving knowledge regarding tumor recurrence in patients with early-stage TSCC.