title: Prognostic value of the chemokine receptor CXCR4 and epithelial-to-mesenchymal transition in patients with squamous cell carcinoma of the mobile tongue.
abstract: OBJECTIVE
  The aim of this study was to evaluate the expression and the prognostic value of chemokine receptor 4 (CXCR4), its cognate ligand the CXCL12, and markers of epithelial-to-mesenchymal transition (EMT) in squamous cell carcinoma (SCC) of the mobile tongue.
  
  
  METHODS
  Patients with primary SCC of the mobile tongue who underwent surgery in our center were screened retrospectively. Patients without prior treatment, who had pre-surgery TNM staging and available tumor samples, were eligible. Protein expression of CXCL12, CXCR4, CA9, E-cadherin, and vimentin was determined by immunohistochemical staining, scored, and correlated with clinical and pathological parameters and overall survival. Multivariate and Cox proportional hazards analyses were performed.
  
  
  RESULTS
  Among 160 patients treated and screened, 47 were analyzed. CXCR4 and CXCL12 expression was high in tumor cells. CXCR4 expression in primary tumor samples was significantly higher in patients with high-grade tumors, lymph node metastases, and microscopic nerve invasion (p ≤ 0.05). There was a non-significant trend towards a correlation between high CXCL12 expression and pathologic tumor stage (p=0.07). Tumors with high CXCR4 expression correlated with poor overall survival (hazard ratio=3.6, 95% confidence interval 1.3-9.7; p=0.011), notably in the CXCR4(high)/vimentin-positive subgroup. Vimentin-positive tumors, characterizing EMT, were associated with lower survival (hazard ratio=4.5, 95% confidence interval 1.6-12.3; p=0.0086). Multivariate analysis confirmed vimentin (but not CXCR4) expression as an independent prognostic factor of poor overall survival (p=0.016).
  
  
  CONCLUSIONS
  Our results suggest that CXCR4 is a marker of tumor aggressiveness and vimentin is an important and independent prognostic factor in patients with SCC of the mobile tongue.
authors: INSERM U728, RayLab, and Departments of Medical Oncology, Beaujon University Hospital (AP-HP - Paris 7 Diderot), Clichy, France.
authors: Sébastien
authors: S
authors: Albert
authors: Muriel
authors: M
authors: Hourseau
authors: Caroline
authors: C
authors: Halimi
authors: Maria
authors: M
authors: Serova
authors: Véronique
authors: V
authors: Descatoire
authors: Béatrix
authors: B
authors: Barry
authors: Anne
authors: A
authors: Couvelard
authors: Maria Eugenia
authors: ME
authors: Riveiro
authors: Annemilaï
authors: A
authors: Tijeras-Raballand
authors: Armand
authors: A
authors: de Gramont
authors: Eric
authors: E
authors: Raymond
authors: Sandrine
authors: S
authors: Faivre
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4