Epithelial-mesenchymal transition modulates lower lip carcinogenesis and promotes cancer progression

Abstract

ObjectiveTo investigate and compare the immunoexpression of E-cadherin, α-SMA, TGF-β and Snail proteins between cases of actinic cheilitis (AC) and squamous cell carcinoma of the lower lip (LLSCC). Study designE-cadherin, α-SMA, TGF-β and Snail antibody immunostaining was analyzed semiquantitatively in 54 AC cases and in 49 LLSCCs. The cases were classified as low and high expression for analysis of the association with clinicopathological variables and overall survival (OS) and disease-free survival (DFS) rates. ResultsHigh expression of E-cadherin (cytoplasmic) (p = 0.001) and α-SMA (p < 0.001) was identified in LLSCCs, as well as low expression of TGF-β in LLSCCs (p < 0.001) and high expression of Snail in AC cases (p = 0.006). Survival analysis revealed that high expression of α-SMA at the tumor invasion front, a network immunostaining pattern of this protein, and high expression of TGF-β in tumor buds were significantly associated with poor OS (p < 0.05). There was a higher risk of death among LLSCC cases with high expression of α-SMA (HR = 5.90, p = 0.03). High expression of TGF-β in tumor buds was significantly associated with poor DFS (p = 0.007) and with a higher risk of negative outcomes for DFS (HR = 4.44, p = 0.014). ConclusionsThe present results suggest the potential involvement of dysregulation of proteins associated with epithelial-mesenchymal transition in the modulation of lip carcinogenesis and greater aggressiveness of LLSCC.