Aberrant expression of nuclear vimentin and related epithelial–mesenchymal transition markers in nasopharyngeal carcinoma

Abstract

Expression of vimentin and the epithelial to mesenchymal transition (EMT) markers E-cadherin, b-catenin is essential for the progression of various human cancers. Our study aimed to investigate the aberrant localization E-cadherin, b-catenin and vimentin, and their prognostic significance in 122 nasopharyngeal carcinoma (NPC) patients by immunohistochemistry and immunofluorescence. Our results showed that both membranous and cytoplasmic localization of E-cadherin staining were associated with lymph node metastasis (p 5 0.000 and 0.005, respectively) and clinical stage (p 5 0.000 and 0.007, respectively). High cytoplasmic b-catenin correlated significantly with larger tumor size (p 5 0.020), lymph node metastasis (p 5 0.000) and advanced clinical stage (p 5 0.036). However, no significant difference was observed between membranous b-catenin and clinicopathologic features (p ! 0.05). High nuclear vimentin expression correlated significantly with positive lymph node metastasis (p 5 0.000) and advanced clinical stage (p 5 0.000). Multivariate analysis showed that nuclear vimentin and cytoplasmic E-cadherin were independent prognostic factors (p 5 0.016 and 0.001, respectively), as well as M classification (p 5 0.001). More importantly, patients with high coexpression of nuclear vimentin and cytoplasmic E-cadherin had shorter survival time (p 5 0.000). Furthermore, high coexpression of these two proteins was closely associated with lymph node metastasis (p 5 0.000) and advanced clinical stage (p 5 0.000). Our studies provide convincing evidence that EMT may play an important role in the biological progression of NPC, and nuclear vimentin and cytoplasmic E-cadherin might have independent prognostic value in NPC patients and serve as novel targets for prognostic therapeutics.Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck cancer with distinct ethnic and geographic distributions. It occurs with the highest frequency in Southern China, with an incidence rate of approximately 20-50 cases per 100,000 people each year.1 In contrast with other head and neck cancers, most cases of NPCs are undifferentiated squamous cell carcinomas with a high tendency to invade adjacent tissues and metastasize to regional lymph nodes at an early stage. Furthermore, the majority deaths of NPC patients are attributed to local recurrence and distant metastases. 2,3 It is known that genetic susceptibility, EpsteinBarr virus (EBV) infection and dietary factors play important roles in NPC pathogenesis. 4 However, the molecular mechanisms mediating the progression and metastasis of NPC have not been fully clarified.Epithelial-mesenchymal transition (EMT) is characterized as loss of epithelial morphology and development of a highly motile mesenchymal phenotype. 5,6 EMT is essential for embryonic development and has recently been demonstrated to be crucial for the invasion and metastasis of tumors, providing tumor cells with the capacity to escape from the primary site and invade the surrounding stroma. [7][8][9] It is well known...

Evaluation of E-cadherin, β-catenin and vimentin protein expression using quantitative immunohistochemistry in nasopharyngeal carcinoma patients

“…Our cohort most closely resembles that reported by Galena et al (n=18) [24] in which there were a greater number of WHO I/II cases, whereas the other two NPC studies were done in Asia where WHO type 3 is predominant [23,25]. We did not observe a difference in outcome by biomarker status when the analyses was stratified by WHO class (1/2 and 3) making this a less likely factor (data not shown).…”

“…More recently, Luo et al also evaluated E-cadherin, β-catenin and vimentin in biopsies in a comparably-sized group (n=122) of NPC patients. As was seen in this study, Luo also reported that the co-expression of high cytoplasmic E-cadherin and high nuclear vimentin, but not β-catenin expression, was correlated with shorter patient survival in multivariate analyses [25].…”

The ratio of transforming growth factor-β1/bone morphogenetic protein-7 in the progression of the epithelial-mesenchymal transition contributes to rat liver fibrosis

“…In the resting state, cultured liver epithelial cells have an epithelioid morphology, but neither FSP-1 nor α-SMA has this morphology (Luo et al, 2012). Treatment with TGF-β1 induces Smad2/3 phosphorylation with translocation of the corresponding phosphoproteins to the nucleus.…”

CD26/dipeptidyl peptidase IV contributes to tumor metastasis in human lung adenocarcinoma

“…Vimentin overexpression in cancer correlates with accelerated tumor growth, invasion, and poor prognosis. In recent years, vimentin has been recognized as a marker for EMT (Vuoriluoto et al, 2011;Satelli and Li, 2011;Luo et al, 2012). As a regulator of cadherin-mediated cell-cell adhesion, β-catenin plays an important role in EMT (Du et al, 2010;Yan et al, 2012;Sánchez-Tilló et al, 2011;Zhao et al, 2011).…”