Epithelial-mesenchymal transition and mesenchymal-epithelial transition via regulation of ZEB-1 and ZEB-2 expression in pancreatic cancer

Background and Objecties Phenotypic plasticity of cancer cells via epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET) is essential for tumor progression and metastasis. Methods Tissue samples were obtained from 76 pancreatic head cancers. We assessed the expression of E-cadherin, vimentin, ZEB-1, and ZEB-2 by immunohistochemical and immunofluorescence staining. Next, 147 metastatic lymph nodes from 45 pancreatic cancers with low expression of E-cadherin were obtained and divided into two categories according to the maximum diameter of the metastases: 2 mm or more and less than 2 mm. Results High expressions of ZEB-1 and ZEB-2 in the primary tumors were significantly associated with repression of E-cadherin (P = 0.0007), and poorer prognosis (P = 0.0322). Forty-three (29.3%) of the 147 metastatic tumors from pancreatic cancers with low expression of E-cadherin showed high E-cadherin expression. Cancer cells in the larger metastases showed high expression of E-cadherin (P = 0.0061) and low expression of ZEB-1 (P = 0.0170) and ZEB-2 (P = 0.0036) compared with those in the smaller metastases. Conclusions In primary pancreatic tumors and metastatic lymph nodes, high and low expression of ZEB-1 and ZEB-2 was associated with mesenchymal and epithelial phenotype of cancer cells, respectively. J. Surg. Oncol. 2012; 105:655–661. © 2011 Wiley Periodicals, Inc.