Association between lymphangiogenesis-/micrometastasis- and adhesion-related molecules in resected stage I NSCLC

Lung Cancer. 2010 Dec;70(3):320-8. doi: 10.1016/j.lungcan.2010.02.013. Epub 2010 Apr 2.


Background: The purpose of this study was to clarify the role and clinical significance of lymphangiogenesis/micrometastases and adhesion molecules in resected stage I non-small cell lung cancer (NSCLC).

Methods: Immunohistochemical (IHC) staining was used to analyze the protein expression of vascular endothelial growth factor-C (VEGF-C), VEGF, E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin in paraffin-embedded tumor samples from 117 well-characterized stage I NSCLC patients and to compare the protein expression, clinical variables and survival outcome. As a micrometastatic parameter in lymph nodes (LNs), cytokeratin (CK) staining was performed.

Results: The positive expression of VEGF-C and VEGF were detected in 54 (48.7%) and 86 (73.5%), respectively. We identified micrometastatic tumor cells in pathological N0 LNs in 34 (29.1%) of 117 patients. E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin were identified in 70 (59.8%), 41 (35.0%), 83 (70.9%), and 61 (52.1%) specimens, respectively. The VEGF-C expression was found more frequently in squamous cell carcinoma (SQ) and in the tumors with negative expression of beta-catenin than counter features. The VEGF expression was found more frequently in the tumors with a negative expression of E-cadherin. Micrometastasis was found more frequently in a pathological T2 status and in the tumors with a negative expression of alpha-catenin. Beta-catenin and gamma-catenin expressions were found less and more frequently in SQ, respectively. A univariate and multivariate survival analysis demonstrated that old age, pathological T2 status, and micrometastasis were independently associated with an increased risk of poor survival in the patients who underwent a surgical resection of stage I NSCLC.

Conclusions: Complicated relationships exist between lymphangiogenesis/micrometastases and adhesion molecules with a specific histology. The detection of lymph nodal micrometastasis by CK may therefore be a useful marker for predicting a poor prognosis in patients who undergo a complete resection of stage I NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Catenins / genetics
  • Catenins / metabolism
  • Cell Adhesion
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Keratins / genetics
  • Keratins / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Lung Neoplasms / surgery
  • Lymph Nodes / metabolism*
  • Lymph Nodes / pathology
  • Lymphangiogenesis
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Vascular Endothelial Growth Factors / genetics
  • Vascular Endothelial Growth Factors / metabolism


  • Biomarkers, Tumor
  • Cadherins
  • Catenins
  • Vascular Endothelial Growth Factors
  • Keratins