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 β-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.
Department of Pathology, Chung-Ang University College of Medicine, 156-756 Seoul, Korea.
Han Suk
HS
Ryu
Do Joong
DJ
Park
Hyung Ho
HH
Kim
Woo Ho
WH
Kim
Hye Seung
HS
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015820:Cadherins; D018960:Hyaluronan Receptors; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin