Epithelial-mesenchymal transition in colorectal cancer tissue of patients with Lynch syndrome.

AIM: To explore the epithelial-mesenchymal transition (EMT) in tissue from patients with Lynch syndrome, and to interpret biological behaviour of Lynch syndrome. METHODS: Sixty-eight formalin-fixed and paraffin embedded tissue blocks were analyzed in this study, including tissues from Lynch syndrome (n = 30), sporadic colorectal carcinoma (CRC) (n = 30), and tumoradjacent tissues (n = 8). Tissue sections were stained for human mutS homolog 2 (hMSH2), human mutL homolog 1 (hMLH1), transforming growth factor-beta type. receptor (TGF beta RII), E-cadherin, beta-catenin, matrix metalloproteinase-7 (MMP-7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) by immunohistochemical staining. Furthermore, clinical data such as age, gender and tumor-node-metastasis stage were also collected retrospectively. RESULTS: The positive expression rates of hMSH2, hMLH1, TGF beta RII, E-cadherin, beta-catenin, MMP-7 and TIMP-2 were significantly related to the depth of invasion and lymph node metastasis, but not to sex or tumour size or location. The differences in the positive expression rates of hMSH2, hMLH1, TGF beta RII, E-cadherin, cytomembrane beta-catenin, cytoplasmic beta-catenin, MMP-7 and TIMP-2 were significant between sporadic CRC and Lynch syndrome. The expression of hMSH2 had a positive correlation with that of hMLH1 in Lynch syndrome and sporadic CRC. The expression of TGF beta RII had a positive correlation with that of hMSH2, hMLH1 and MMP-7, and a negative correlation with that of TIMP-2. The expression of MMP-7 had a negative correlation with that of TIMP-2 in Lynch syndrome and sporadic CRC. The expression of E-cadherin was positively correlated with that of cytomembrane beta-catenin. However, the expression of cytomembrane beta-catenin was negatively correlated with that of cytoplasmic beta-catenin, and the expression of cytoplasmic beta-catenin was positively correlated with that of MMP-7. CONCLUSION: EMT may play an important role in the development and progression of Lynch syndrome. Lynch syndrome was caused by the mutations of mismatch repair genes, mainly hMSH2 and hMLH1, which also beget the mutational inactivation of TGF beta RII. Therefore, the colorectal cancer of Lynch syndrome can escape the inhibitory effect of TGF beta 1. However, TGF beta 1 can up-regulate the expression of MMP-7 and down-regulate the expression of TIMP-2 in tumors by disassembling the E-cadherin/beta-catenin complex in the cytomembrane. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.