title: Immunohistochemical evaluation of CXCL12-CXCR4 axis and VEGFR3 expression in primary urothelial cancer and its recurrence.
abstract: OBJECTIVE
  The aim of this study was to investigate the expression of CXC chemokine ligand-12 (CXCL12), CXC chemokine receptor 4 CXCR4 and of vascular endothelial growth factor receptor 3 (VEGFR3) in primary urothelial bladder carcinoma and their recurrence in relation to grade and pT status.
  
  
  METHODS
  Immunohistochemistry was applied to 67 primary tumor (PC) sections and their recurrenct tumors (RC).
  
  
  RESULTS
  The expression of CXCL12 both in PC and in RC was positively associated with tumor grade (p<0.0001 and p<0.0001, respectively) and pT stage (p=0.001 and p=0.007, respectively). The expression of CXCR4 in both PC and RC was also positively related to grade (p=0.001 and p<0.0001, respectively) and pT stage (p=0.008 and p=0.005, respectively). We compared the expression of CXCL12 and CXCR4 in PC related to RC and found that both were more intense in RC than in PC (p<0.0001 and p<0.0001, respectively). In PC and in RC there was no association between the expression of VEGFR3 with tumor grade and pT stage.
  
  
  CONCLUSIONS
  CXCL12 and CXCR4 expression was related to adverse prognostic markers in urothelial bladder carcinoma through their association with grade and pT stage both in PC and RC. The CXCL12-CXCR4 axis may influence the expression of VEGFR3 in urothelial bladder carcinoma and promote tumor recurrence.
authors: Department of Pathology, Syggros Venereal and Skin Disease Hospital Athens, Athens, Greece rania.mpatsi@gmail.com.
authors: Ourania
authors: O
authors: Batsi
authors: First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors: Ioanna
authors: I
authors: Giannopoulou
authors: Department of Pathology, Syggros Venereal and Skin Disease Hospital Athens, Athens, Greece.
authors: Ioannis
authors: I
authors: Nesseris
authors: Department of Pathology Metaxa Cancer Hospital, Piraeus, Greece.
authors: Christos
authors: C
authors: Valavanis
authors: First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors: Hariklia
authors: H
authors: Gakiopoulou
authors: First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors: Efstratios S
authors: ES
authors: Patsouris
authors: Department of Pathology Metaxa Cancer Hospital, Piraeus, Greece.
authors: Petroula
authors: P
authors: Arapandoni-Dadioti
authors: First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors: Andreas C
authors: AC
authors: Lazaris
mesh_terms: D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009367:Neoplasm Staging; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis*
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: CXCL12; CXCR4; VEGFR-3; recurrence; urothelial cancer