Immunohistochemical expression of angiogenesis-related markers in oral squamous cell carcinomas with multiple metastatic lymph nodes

Am J Clin Pathol. 2003 Apr;119(4):574-86. doi: 10.1309/JD3D-HGCD-GAUN-1R0J.


The aim of this study was to evaluate the histopathologic features and the expression of angiogenesis-related markers in primary tumors and metastatic lymph nodes of oral squamous cell carcinomas (SCCs) with multiple lymph node involvement in comparison with oral SCCs without nodal metastasis. The protein levels of the angiogenesis inhibitor endostatin, as well as those of the related molecules collagen XVIII, collagen-binding protein (CBP) 2/heat shock protein (HSP) 47, and cathepsin L, were evaluated by immunohistochemical analysis. Compared with nonmetastatic cases, primary tumors of the metastatic group exhibited significantly decreased protein levels of endostatin and its precursor collagen XVIII. Comparison between primary tumors and positive nodes of the metastatic cases revealed decreased expression of collagen XVIII and CBP2/HSP47 in metastases. Angiogenesis is essential for tumor growth and metastasis; accordingly, the observed differences in the immunohistochemical expression of angiogenesis-related proteins in oral SCC with multiple lymph node involvement may provide an explanation for the increased metastatic potential of these tumors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / secondary
  • Carrier Proteins / metabolism
  • Cathepsin L
  • Cathepsins / metabolism
  • Collagen / metabolism
  • Collagen Type XVIII
  • Cysteine Endopeptidases
  • Endostatins
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Glycoproteins
  • Humans
  • Immunoenzyme Techniques
  • Lymph Nodes / metabolism*
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Neoplasm Metastasis / pathology
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Peptide Fragments / metabolism


  • Biomarkers, Tumor
  • Carrier Proteins
  • Collagen Type XVIII
  • Endostatins
  • Glycoproteins
  • Peptide Fragments
  • colligin
  • Collagen
  • Cathepsins
  • Cysteine Endopeptidases
  • CTSL protein, human
  • Cathepsin L