Combination of epithelial-mesenchymal transition and cancer stem cell-like phenotypes has independent prognostic value in gastric cancer

Epithelial-mesenchymal transition related proteins have been suggested to interact with each other in various cancers and be associated with the aggressive behavior of cancer. To demonstrate the clinical significance of epithelial-mesenchymal transition and stem cell like phenotypes in gastric cancer, we performed immunohistochemistry for 5 epithelial-mesenchymal transition related proteins, including Snail-1, ZEB-1, E-cadherin, vimentin, and beta-catenin, and the gastric cancer stem cell marker CD44 in 276 consecutive primary gastric cancers and 54 matched lymph node metastases. Loss of E-cadherin expression and aberrant expression of vimentin were significantly associated with aggressive clinicopathologic features. The expression of epithelial-mesenchymal transition related proteins was closely related to each other in gastric cancer. The known gastric cancer stem cell maker, CD44, was significantly associated with the protein expression of Snail-1, ZEB-1, and E-cadherin (P < .05). Univariate survival analysis was performed for the 6 proteins included in this study to find the best combination for predicting patient outcome. Protein expression of Snail-1, vimentin, E-cadherin, and CD44 resulted in the lowest P value using the Kaplan-Meier method (P < .001). This combination of proteins was significantly associated with advanced pT stage, lymph node metastasis, vascular invasion, and undifferentiated histologic type in a high-risk group (P < .001) and predicted disease-free survival independent of pTNM stage and histologic differentiation (P = .029). However, the acquired mesenchymal phenotype of gastric cancer cells at the primary site was restored to an epithelial phenotype in lymph node metastases. A combination of epithelial-mesenchymal transition and stem cell like phenotypes is an important predictor of aggressive biologic behavior and has an independent prognostic value in predicting outcomes of primary gastric cancer. (C) 2012 Elsevier Inc. All rights reserved.