title: Lymphangiogenesis in regional lymph nodes predicts nodal recurrence in pathological N0 squamous cell carcinoma of the tongue.
abstract: OBJECTIVE
  Cancer cells induce de-novo lymphatic vessel growth within draining lymph nodes before they metastasize. The aim of this study was to retrospectively evaluate lymph node lymphangiogenesis before the establishment of nodal recurrence in squamous cell carcinoma (SCC) of the tongue.
  
  
  RESULTS
  Surgical specimens from 28 patients with pT2-T3N0M0 SCC of the tongue after local excision with supraomohyoid neck dissection were studied by immunohistochemistry. Intranodal lymphatic endothelium was highlighted by podoplanin staining to evaluate lymphatic vessel counts (LVCs). Primary tumour sections were examined for the expression of lymphangiogenic factors: vascular endothelial growth factor (VEGF)-C and VEGF-D. LVCs in regional lymph nodes were significantly increased in the cases with nodal recurrence (P=0.0013). Simultaneous increases in VEGF-C and VEGF-D expression were significantly associated with both an increase in LVC in regional lymph nodes (P=0.0001) and a decrease in the rate of survival without nodal recurrence (P=0.016).
  
  
  CONCLUSIONS
  Knowing the status of lymphangiogenesis in the regional pN0 lymph nodes in tongue cancer would help in predicting which patients will develop nodal recurrence. The use of a therapeutic approach which blocks lymphangiogenic factors, such as VEGF-C and VEGF-D, may be beneficial in suppressing the lymphatic spread of tongue cancer with intense intranodal lymphangiogenesis.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hirota
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wakisaka
authors.forename: Seiko
authors.initials: S
authors.lastname: Sawada-Kitamura
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Murono
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012008:Recurrence; D012189:Retrospective Studies; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism
chemical_list: D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D