ABSTRACT
Background: Oral squamous cell carcinoma (OSCC) accounts for 90% of oral malignancies, which may be preceded by oral potentially malignant disorders (OPMDs). Cancer progression involves the downregulation of epithelial markers (E-cadherin) and the upregulation of mesenchymal markers (N-cadherin), which together characterise the epithelial-mesenchymal transition (EMT). Furthermore, caveolin can act on cell adhesion and migration events that regulate the expression of the E-cadherin/α-ß-catenin complex, thus favouring aggressive biological behaviour. This study aimed to analyse the immunoexpression of E-cadherin, N-cadherin and caveolin-2 at different stages of oral carcinogenesis to identify reliable biomarkers to predict malignant potential. Methods: Expressions of E-cadherin and N-cadherin in 14 normal oral mucosae (NOM), 14 OPMD and 33 OSCC specimens were evaluated using immunohistochemistry. Clinicopathological parameters were also assessed. Results: E-cadherin immunoexpression was significantly reduced during the progression of oral carcinogenesis (P = 0.0018). N-cadherin immunoexpression did not show any statistical differences between these groups. However, a representative number of N-cadherin-positive OSCC cases did not express E-cadherin. The expression of caveolin-2 increased significantly with the progression of the disease, from NOM to OSCC (P value: 0.0028). Conclusion: These findings indicate that cadherin switch and caveolin-2 immunoexpression may be regulatory events in oral carcinogenesis.
ABSTRACT
Myofibroblasts are differentiated contractile cells that can secrete extracellular matrix components, cytokines, proteases, and proangiogenic factors. In neoplastic processes such as oral squamous cell carcinoma (OSCC), myofibroblasts are recognized as cancer-associated fibroblasts (CAFs) and actively participate in tumor progression. As the presence of myofibroblasts in the stroma may be an important parameter of invasion and proliferation, the aim of this study was to evaluate the presence of CAFs in OSCC by immunophenotyping and their association with histologic classification and clinicopathologic parameters. A total of 34 formalin-fixed, paraffin-embedded samples of OSCC were analyzed for CAF histology and immunophenotype established on the basis of the simultaneous immunohistochemical expression of α-SMA, fibronectin, FSP1, HHF35, and vimentin. According to the histologic classification of CAFs, 16 (47%) cases were classified as the mature subtype and 18 (53%) as the immature subtype. CAF immunophenotype was detected in 19 (56%) cases, and the immunophenotype was variable in 15 (44%) cases. The CAFs immunophenotype was significantly associated with the immature histologic subtype. Immunohistochemical expression of α-SMA, fibronectin, FSP1, HHF35, and vimentin represents a suitable CAF immunophenotype in OSCC. The CAF immunophenotype is associated with the immature histologic subtype. The characterization of CAFs may identify tumors with a distinct biological profile in OSCC. Studies extending the investigation of CAFs to OSCC are needed to determine the actual role of this cell population as a possible prognostic marker.
