title: Tumour expression of lymphangiogenic growth factors but not lymphatic vessel density is implicated in human cervical cancer progression.
abstract: OBJECTIVE
  The aim of the study was to investigate the role of lymphangiogenesis in human cervical cancer progression.
  
  
  METHODS
  The expression of VEGF-C, VEGF-D, VEGFR-3, podoplanin (D2-40), LYVE-1 and Prox-1 was studied by immunohistochemistry in 72 cases of invasive squamous cell carcinoma of the uterine cervix. For lymphatic endothelial markers lymphatic vessel density (LVD) was assessed. Correlations with lymphatic vessel invasion, nodal metastases, tumour grade, FIGO stage, and inflammation were also evaluated.
  
  
  RESULTS
  VEGF-D expression significantly correlated with lymph node metastasis, lymphatic emboli and FIGO stage as well as with peritumoural LVD. A marginally significant correlation was also found between the expression of VEGF-C and prognostic parameters. Lymphatic tumour emboli were successfully identified using D2-40 immunohistochemistry and peritumoural D2-40 LVD significantly correlated with lymphatic vessel invasion. However, LVD as assessed by multiple lymphatic markers was not associated with lymphatic metastasis. There was a significant correlation of Prox-1 and LYVE-1 LVD with the inflammatory stromal reaction.
  
  
  CONCLUSIONS
  Although LVD as assessed by multiple lymphatic markers was not correlated with prognostic parameters, tumour expression of lymphangiogenic growth factors seems to be critically implicated in lymphatic metastasis and cervical carcinoma progression.
authors.affiliation: Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Nikolia
authors.initials: N
authors.lastname: Sotiropoulou
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Bravou
authors.forename: Sofia
authors.initials: S
authors.lastname: Kounelis
authors.forename: Vasileia
authors.initials: V
authors.lastname: Damaskou
authors.forename: Eirini
authors.initials: E
authors.lastname: Papaspirou
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
mesh_terms: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000378:metabolism; D009367:Neoplasm Staging; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis; D033921:Vesicular Transport Proteins / Q000096:biosynthesis; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C119248:LYVE1 protein, human; D025521:Tumor Suppressor Proteins; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D033921:Vesicular Transport Proteins; C500987:monoclonal antibody D2-40; D000098551:Prospero-Related Homeobox 1 Protein; D040321:Vascular Endothelial Growth Factor Receptor-3