Abstract: Background and purpose: Tumor-infiltrating regulatory T cells (Tregs) play an important role in the development of various cancers, Epithelial-mesenchymal transition (EMT) is a key step toward cancer metastasis, but the interaction between Tregs and EMT has not yet been evaluated. We aimed to investigate the relationship of FoxP3+ Tregs and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) and to determine the clinical significance of Tregs. Methods: Seventy-four sets of patient-matched tumors and twenty sets of peritumoral tissues were obtained during curative resection for HCC. The expression of FoxP3, E-cadherin, Vimentin protein and Snail mRNA was detected by immunohistochemistry and in situ hybridization histochemistry in formalin-fixed and paraffin-embedded tissues. Results: The average number of intratumoral Tregs was significantly higher than that in corresponding peritumoral tissues [9.7 (3.8-20.2) vs 1.4 (0.5-4.2), respectively; P<0.01]. The number of intratumoral Tregs was positively correlated with potal vein tumor thrombus and microvascular invasion (P<0.05). Increased number of intratumoral Tregs was significantly associated with decreased rates of recurrence-free and overall survival (P<0.05, P<0.01). There was a significant negative correlation between E-cadherin and the other EMT-related markers (Vimentin: r=-0.572, P<0.01, Snail: r=-0.597, P<0.01). Increased number of intratumoral Tregs was characterized by increased expression of EMT-related proteins (Vimentin: r=0.598, P<0.01; Snail: r=0.423, P<0.05) and loss of E-cadherin expression(r=-0.513, P<0.05). Conclusion: Intratumoral infiltration by Tregs is closely related to metastasis and EMT
in HCC, FoxP3+ Tregs may be a potential prognostic indicator for HCC patients.

Key words: Hepatocellular neoplasms, Hepatocellular carcinoma, Tregs, Epithelial mesenchymal transition