Abstract
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.
Highlights
In China, esophageal squamous cell carcinomas (ESCCs) account for most malignant esophageal tumors [1]
We classified the Epithelial-mesenchymal transition (EMT) phenotypes of primary tumors (PTs) and metastatic lymph nodes (MLNs) in a cohort of T3N1-3M0 ESCC patients based on the expression pattern of EMT-related markers
We observed a loss of E-cadherin expression in 51.6% of T3N1-3 ESCC PTs and gain of N-cadherin and vimentin expression in 65.3% and 43.7%, respectively
Summary
In China, esophageal squamous cell carcinomas (ESCCs) account for most malignant esophageal tumors [1]. Due to the heterogeneity of tumor cells at the primary site or selection pressure during tumor metastasis, genotypes and gene and protein expression may differ between the primary tumor (PTs) and metastatic lymph nodes (MLNs) in ESCCs, as well as other cancer types [3,4,5,6,7]. These underlying molecular differences lead to differences in the biological characteristics of PTs and their metastases. Activation of vimentin expression, which alters the composition of intermediate filaments, is frequently used as a mesenchymal marker in cancer [11]
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