title: Combined aberrant expression of E-cadherin and S100A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients.
abstract: OBJECTIVE
  Epithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients.
  
  
  METHODS
  We evaluated the expression of E-cadherin, β-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, β-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR.
  
  
  RESULTS
  Loss of E-cadherin, nuclear β-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, β-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not β-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of β-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation.
  
  
  CONCLUSIONS
  The combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups.
authors.affiliation: Department of Surgery, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Sang-Jeon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Choi
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Meiying
authors.initials: M
authors.lastname: Ji
authors.forename: Taek-Gu
authors.initials: TG
authors.lastname: Lee
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Son
authors.forename: Soon Man
authors.initials: SM
authors.lastname: Yoon
authors.forename: Rohyun
authors.initials: R
authors.lastname: Sung
authors.forename: Eun Jeoung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Sei Jin
authors.initials: SJ
authors.lastname: Youn
authors.forename: Seon Mee
authors.initials: SM
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000517:prevention & control; D011379:Prognosis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D051176:beta Catenin; C077591:S100A4 protein, human