The epithelial-mesenchymal transition phenotype of metastatic lymph nodes impacts the prognosis of esophageal squamous cell carcinoma patients
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Jing Wen1,2,*, Kong-Jia Luo1,2,3,*, Qian-Wen Liu1,2,3, Geng Wang4, Mei-Fang Zhang5, Xiu-Ying Xie1,2, Hong Yang1,2,3, Jian-Hua Fu1,2,3, Yi Hu1,2,3
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
2Guangdong Esophageal Cancer Institute, Guangzhou 510060, China
3Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
4Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou 515041, China
5Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
*These authors contributed equally to this work and share first authorship
Jianhua Fu, email: [email protected]
Yi Hu, email: [email protected]
Keywords: esophageal squamous cell carcinoma, epithelial-mesenchymal transition, metastatic lymph node, prognosis
Received: July 25, 2015 Accepted: April 7, 2016 Published: April 27, 2016
Epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis, but the significance of EMT phenotype to the prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. We used immunohistochemistry to examine the expression of the EMT-related proteins E-cadherin, N-cadherin and vimentin in samples of T3N1-3M0 ESCC from 155 primary tumors (PTs) with paired metastatic lymph nodes (MLNs) and 58 PTs without paired MLNs. Based on the expression pattern of the EMT markers, PTs and MLNs were classified as EMT wild, hybrid, null or complete type. The hybrid (42.7%) and complete (39.4%) types predominated among PTs, whereas the wild (34.2%) and hybrid (52.9%) types predominated among MLNs, and EMT phenotypes differed between the paired PTs and MLNs (P < 0.001). Univariate analysis revealed that, for PTs, the EMT phenotype was associated with N-stage (P = 0.039) but not patient survival, and that patients with complete or hybrid type MLNs had better overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.005) than patients with null and wild type MLNs, especially those with N1-stage disease (P = 0.017 for OS, and P = 0.017 for DFS, respectively). Multivariate analysis revealed that wild and null type MLNs as well as older age and N2-3 stage were independent predictors of OS and DFS (P < 0.05). Thus MLNs exhibit EMT phenotypes that are distinct from those of their PT and may serve as a novel independent prognostic indicator in ESCC.
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