Department of Pathology, Chung-Ang University College of Medicine, 156-756 Seoul, Korea.
Hum Pathol. 2012 Apr;43(4):520-8. doi: 10.1016/j.humpath.2011.07.003. Epub 2011 Oct 21.
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.
上皮-间质转化相关蛋白已被证实相互作用于多种癌症，并与癌症的侵袭性行为相关。为了证明上皮-间质转化和肿瘤干细胞样表型在胃癌中的临床意义，我们对 276 例连续原发性胃癌和 54 例配对淋巴结转移标本进行了 5 种上皮-间质转化相关蛋白（包括 Snail-1、ZEB-1、E-钙黏蛋白、波形蛋白和β-连环蛋白）和胃癌干细胞标志物 CD44 的免疫组织化学染色。E-钙黏蛋白表达缺失和波形蛋白异常表达与侵袭性临床病理特征显著相关。在胃癌中，上皮-间质转化相关蛋白的表达彼此密切相关。已知的胃癌干细胞标志物 CD44 与 Snail-1、ZEB-1 和 E-钙黏蛋白的蛋白表达显著相关（P<0.05）。我们对本研究中包含的 6 种蛋白进行了单因素生存分析，以找到预测患者预后的最佳组合。用 Kaplan-Meier 法发现，Snail-1、波形蛋白、E-钙黏蛋白和 CD44 的蛋白表达具有最低的 P 值（P<0.001）。这组蛋白与高危组中更晚期的 pT 分期、淋巴结转移、血管侵犯和未分化组织学类型显著相关（P<0.001），并独立于 pTNM 分期和组织学分化预测无病生存（P=0.029）。然而，胃癌细胞在原发部位获得的间质表型在淋巴结转移中又恢复为上皮表型。上皮-间质转化和肿瘤干细胞样表型的组合是侵袭性生物学行为的重要预测因子，对预测原发性胃癌的预后具有独立的价值。
