Increased vascular endothelial growth factor and vascular endothelial growth factor-c and decreased nm23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer

J Thorac Cardiovasc Surg. 2000 Apr;119(4 Pt 1):804-13. doi: 10.1016/S0022-5223(00)70017-1.


Objective: We examined a microdissemination of cancer cells in lymph nodes and assessed its clinical and biologic characteristics.

Methods: Both primary tumors and lymph nodes (2030 nodes) were obtained from 122 patients with primary stage I lung cancer who underwent curative operations with routine systematic nodal dissection of both the hilar and the mediastinal nodes. Immunohistochemical anticytokeratin staining was used to detect nodal microdissemination of cancer cells. Vascular endothelial growth factor, vascular endothelial growth factor type C, and nm23 expression at primary sites were also immunohistochemically studied.

Results: In total, 35 patients (29%) had cytokeratin-positive cells in lymph nodes. Increased expression of vascular endothelial growth factor (P =.0001) and vascular endothelial growth factor type C (P <. 0001) at primary sites were significantly associated with nodal microdissemination, and nm23 was inversely correlated with microdissemination (P =.008). The 3- and 5-year survivals for the patients with nodal microdissemination were 57% and 54%, respectively, which was a significantly worse prognosis as compared with those prognoses (83% and 76%) for the patients without nodal microdissemination (P =.006). The independent prognostic impact of nodal microdissemination was not clear; however, vascular endothelial growth factor retained independent significance.

Conclusion: All of these findings lead us to conclude that the microspread of tumor cells in nodes detected by immunohistochemical anticytokeratin staining is definitely a metastasis with a high risk of systemic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Endothelial Growth Factors / analysis*
  • Female
  • Humans
  • Immunohistochemistry
  • Keratins / analysis
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lymph Nodes / chemistry*
  • Lymphatic Metastasis
  • Lymphokines / analysis*
  • Male
  • Middle Aged
  • Monomeric GTP-Binding Proteins / analysis*
  • NM23 Nucleoside Diphosphate Kinases
  • Nucleoside-Diphosphate Kinase*
  • Prognosis
  • Survival Rate
  • Transcription Factors / analysis*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factors


  • Biomarkers, Tumor
  • Endothelial Growth Factors
  • Lymphokines
  • NM23 Nucleoside Diphosphate Kinases
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factors
  • Keratins
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins