Lymphatic vessel density is not associated with lymph node metastasis in non-small cell lung carcinoma

Arch Pathol Lab Med. 2008 Dec;132(12):1882-8. doi: 10.5858/132.12.1882.


Context: Angiogenesis is essential for tumors to grow and metastasize. Lymphatic metastasis is also an important means of tumor spread. In non-small cell lung carcinoma, the relationship of lymphangiogenesis with lymph node metastasis and, ultimately, patient prognosis is unknown.

Objective: To evaluate whether lymphangiogenesis is related to lymph node metastasis and/or overall survival.

Design: Seventy-eight cases of non-small cell lung carcinoma diagnosed from 1987 to 2004 were retrospectively analyzed for intratumoral, peritumoral, and uninvolved adjacent lung tissue lymphatic vessel density (LVD) by D2-40 immunostaining. Lymphatics in 6 cases of squamous dysplasia/carcinoma in situ were similarly evaluated. Appropriate statistical methods were used.

Results: Intratumoral and peritumoral LVD was significantly higher than in the uninvolved adjacent lung but showed no significant association with lymph node stage at the time of tumor resection. Survival in patients with above average D2-40 values was not significantly different when compared with those who had below average values (median survival, 895 vs 1131 days; P = .97). Furthermore, patients with affected lymph nodes had significantly shorter survival (median survival, 467 vs 1425 days; P = .002). Overall, regardless of lymph node status, there was a significantly higher intratumoral (P < .001) and peritumoral (P < .001) LVD when compared with the adjacent uninvolved lung LVD. There was a trend toward increasing LVD with higher grade of squamous dysplasia.

Conclusions: The results suggest that although lymphangiogenesis occurs in association with non-small cell lung carcinoma, it may not be an important factor in lymph node metastasis. In fact, there is a suggestion that the number of lymphatics that a person inherently has appears to be more important than lymphangiogenesis when it comes to the development of lymph node metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal, Murine-Derived
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology*
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology*
  • Lymphangiogenesis / physiology*
  • Lymphatic Metastasis / physiopathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / metabolism
  • Vesicular Transport Proteins / metabolism


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • LYVE1 protein, human
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Vesicular Transport Proteins
  • monoclonal antibody D2-40