title: Epithelial-mesenchymal transition in colorectal cancer tissue of patients with Lynch syndrome.
abstract: OBJECTIVE
  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 tumor-adjacent tissues (n = 8). Tissue sections were stained for human mutS homolog 2 (hMSH2), human mutL homolog 1 (hMLH1), transforming growth factor-β type II receptor (TGFβRII), E-cadherin, β-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, TGFβRII, E-cadherin, β-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, TGFβRII, E-cadherin, cytomembrane β-catenin, cytoplasmic β-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 TGFβRII 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 β-catenin. However, the expression of cytomembrane β-catenin was negatively correlated with that of cytoplasmic β-catenin, and the expression of cytoplasmic β-catenin was positively correlated with that of MMP-7.
  
  
  CONCLUSIONS
  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 TGFβRII. Therefore, the colorectal cancer of Lynch syndrome can escape the inhibitory effect of TGFβ1. However, TGFβ1 can up-regulate the expression of MMP-7 and down-regulate the expression of TIMP-2 in tumors by disassembling the E-cadherin/β-catenin complex in the cytomembrane.
authors.affiliation: Guo-Li Gu, Xue-Ming Wei, Shi-Lin Wang, Department of General Surgery, the Air Force General Hospital PLA, Beijing 100142, China.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Gu
authors.affiliation: Guo-Li Gu, Xue-Ming Wei, Shi-Lin Wang, Department of General Surgery, the Air Force General Hospital PLA, Beijing 100142, China.
authors.forename: Xiao-Quan
authors.initials: XQ
authors.lastname: Zhu
authors.affiliation: Guo-Li Gu, Xue-Ming Wei, Shi-Lin Wang, Department of General Surgery, the Air Force General Hospital PLA, Beijing 100142, China.
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Wei
authors.affiliation: Guo-Li Gu, Xue-Ming Wei, Shi-Lin Wang, Department of General Surgery, the Air Force General Hospital PLA, Beijing 100142, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Guo-Li Gu, Xue-Ming Wei, Shi-Lin Wang, Department of General Surgery, the Air Force General Hospital PLA, Beijing 100142, China.
authors.forename: De-Chang
authors.initials: DC
authors.lastname: Li
authors.affiliation: Guo-Li Gu, Xue-Ming Wei, Shi-Lin Wang, Department of General Surgery, the Air Force General Hospital PLA, Beijing 100142, China.
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Epithelial-mesenchymal transition; Lynch syndrome; Mismatch repair gene; Mutation; β-catenin