Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)

Abstract

BackgroundElucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis.MethodsProtein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA). We evaluated associations with clinicopathological parameters and prognosis.ResultsThere were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04) and overall survival (OS) (69.6% versus 44.3%, p = 0.05). Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards significance for OS.ConclusionsThe putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis.

Epithelial–Mesenchymal Transition in Non Small-cell Lung Cancer

“…Higher expression of vimentin in tumor samples implies a more aggressive type of tumor and a worse overall survival. These data confirm the role of EMT process in the evaluation of lung cancer and are similar to other studies in several cancer types including NSCLC cell lines, colorectal, thyroid, head and neck and bladder cancer (31)(32)(33)(34)(35)(36). Moreover, low E-cadherin expression was significantly correlated with tumor necrosis (p=0.019).…”

Epithelial‐Mesenchymal Transition: Clinical Implications for Nodal Metastasis and Prognosis of Tongue Cancer

“…15,18,35,36 And the recent study shows that E-cadherin is an independent predictor of improved overall survival using automated quantitative protein analysis. 37 However, recent studies report inconsistent findings for the relationship between expression of Ecadherin in oral cancer and clinical outcomes. 25,36,38 In present study, nodal metastasis and complete EMT type were independent risk factors of DFS after multivariate analysis.…”

Upregulation of osteoprotegerin expression correlates with bone invasion and predicts poor clinical outcome in oral cancer

“…In cancer cells, activation of RANKL/RANK signaling induces epithelial-mesenchymal transition (EMT), which is characterized by the loss of E-cadherin-induced cell-cell contacts and apical-basal polarization, as well as increased cell motility, thus mediates tumor cell migration, invasion and metastasis [15,16]. Evidence indicates that OPG has the ability to bind to and neutralize the apoptotic function of TNF-related apoptosis-inducing ligand (TRAIL) [17].…”