Lymphangiogenesis in regional lymph nodes predicts nodal recurrence in pathological N0 squamous cell carcinoma of the tongue

Histopathology. 2012 Dec;61(6):1065-71. doi: 10.1111/j.1365-2559.2012.04341.x. Epub 2012 Sep 10.

Abstract

Aims: 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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Female
  • Humans
  • Lymph Nodes / pathology*
  • Lymphangiogenesis / physiology*
  • Lymphatic Vessels / pathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Recurrence
  • Retrospective Studies
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology*
  • Vascular Endothelial Growth Factor C / metabolism
  • Vascular Endothelial Growth Factor D / metabolism

Substances

  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D