title: Immunoexpression of VEGFR-3, but not the immunoexpression of VEGF-C or lymphatic density, is correlated with metastasis in lower lip squamous cell carcinoma.
abstract: The purpose of this study was to evaluate the immunoexpression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3) and their correlation with intratumoural lymphatic density (ILD) and peritumoural lymphatic density (PLD) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty-five LLSCC with regional nodal metastasis and 25 LLSCC without metastasis were selected. The percentages of VEGF-C and VEGFR-3 staining in each tumour core and at the deep invasive front were assessed. PLD and ILD were determined using anti-podoplanin antibody. Immunohistochemical findings were correlated with nodal metastasis, clinical staging, local recurrence, clinical outcome, and histological grade. Cytoplasmic immunoexpression of VEGFR-3 in the tumour core was associated with metastasis (P=0.009), patient death (P=0.008), and histological grade (P<0.005). PLD, ILD, and VEGF-C expression showed no significant associations with clinicopathological parameters (P>0.05). PLD and ILD were not significantly correlated with the immunoexpression of VEGF-C or VEGFR-3 (P>0.05). There was a significant positive correlation between PLD and ILD (P=0.004), and between cytoplasmic immunoreactivity of VEGF-C and VEGFR-3 (P=0.011). These results suggest an important role for VEGFR-3 in the progression of LLSCC, and highlight the possible influence of its expression on the prognosis of these tumours. ILD and PLD may not be associated with lymph node metastasis in LLSCC.
authors.affiliation: Dentistry Department, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. Electronic address: anarafaela.luz@terra.com.br.
authors.forename: A R L
authors.initials: AR
authors.lastname: de Aquino
authors.affiliation: Dentistry Department, State University of Paraíba, Campina Grande, Paraíba, Brazil.
authors.forename: C F W
authors.initials: CF
authors.lastname: Nonaka
authors.affiliation: Dentistry Department, Federal University of Campina Grande, Patos, Paraíba, Brazil.
authors.forename: C H P
authors.initials: CH
authors.lastname: de Carvalho
authors.affiliation: Oral Pathology Department, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: C F
authors.initials: CF
authors.lastname: Demeda
authors.affiliation: Oral Pathology Department, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: L B
authors.initials: LB
authors.lastname: de Souza
authors.affiliation: Oral Pathology Department, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: L P
authors.initials: LP
authors.lastname: Pinto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008048:Lip Neoplasms / Q000276:immunology* / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D042582:Vascular Endothelial Growth Factor C / Q000276:immunology*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000276:immunology*; D000098853:Podoplanin
chemical_list: D008562:Membrane Glycoproteins; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: VEGF-C; VEGFR-3; immunohistochemistry; lower lip; lymphangiogenesis; squamous cell carcinoma