BIOMARKERS OF EPITHELIO-MESENCHYMAL TRANSITION IN POTENTIALLY MALIGNANT DISORDERS AND ORAL TONGUE SQUAMOUS CELL CARCINOMA
Squamous cell carcinoma. Epithelial-Mesenchymal Transition. Transcription Factors. Prognosis.
During oral carcinogenesis, malignant cells acquire an aggressive phenotype that results in increased individual motility and the ability to invade surrounding tissues. Therefore, malignant epithelial cells develop a regulatory and programmed process called epithelial-mesenchymal transition (EMT), which is crucial for the acquisition of this aggressive malignant phenotype. The aim of the present study was to investigate the role of immunohistochemical expression of EMT signaling proteins in oral epithelial dysplasia and oral tongue squamous cell carcinoma (OTSCC), evaluating their respective associations with clinical-pathological parameters of prognosis. For the immunohistochemical study, 47 cases of oral epithelial dysplasia and 41 cases diagnosed as (OTSCC) were selected, in which the immunoexpression of the proteins Twist1, Snail1, E-cadherin and N-cadherin were analyzed. Possible associations between the expression pattern of these proteins with the histopathological gradation of epithelial dysplasias and with the clinical-pathological aspects, recurrence and survival in OTSCC were investigated. Different labeling patterns were observed between the analyzed groups, with a significant loss of membrane E-cadherin expression in cases of OTSCC compared to cases of oral epithelial dysplasia (p = <0.0001). A worse overall survival was observed in cases with low membrane E-cadherin expression (HR = 0.27; p = 0.033) and high cytoplasmic Twist1 expression (HR = 3.19; p = 0.010). When analyzing the expression intensity parameter alone, an association was observed between the high intensity of cytoplasmic N-cadherin and overall survival (HR = 4.93; p=0.006). Our findings suggest that loss of E-cadherin expression and increased expression of N-cadherin and nuclear transcription factors Twist1 and Snail1 are associated with the development and progression of oral carcinogenesis. In isolation, loss of membrane expression of E-cadherin and increased cytoplasmic expression of Twist1 and N-cadherin were associated with poorer survival.