Angiogenesis in renal cell carcinoma: Evaluation of microvessel density, vascular endothelial growth factor and matrix metalloproteinases

Int J Urol. 2002 Sep;9(9):509-14. doi: 10.1046/j.1442-2042.2002.00511.x.


Background: Angiogenesis, the growth of new blood vessels, has a critical role in tumor growth and metastasis. The purpose of this study was to investigate the involvement of angiogenesis and angiogenic factors in the pathogenesis of renal cell carcinoma (RCC).

Methods: Formalin-fixed and paraffin-embedded tissue blocks from 70 patients with RCC were studied. The situations of tumor angiogenesis were evaluated by assessing microvessel density (MVD) through CD31 immunostaining. The expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was detected immunohistochemically.

Results: The value of MVD ranged from 12.0 to 93.0 with a median of 39.91 in RCC. Of the 70 RCCs, the expression of VEGF was detected in 52 (74.3%), MMP-2 in 29 (41.4%) and MMP-9 in 19 (27.1%) cases. Statistical analysis revealed significant associations of the tumor stage with MVD, and the expression of VEGF and MMP-2 in RCC. Additionally, MVD was closely related to the expression of VEGF but was not related to the expression of MMP-2 and MMP-9 in RCC.

Conclusion: The degree of angiogenesis may be closely related to the tumor progression of RCC. The expression of VEGF may be responsible for angiogenesis in RCC, and both VEGF and MMP-2 expression may function as tumor associated angiogenic factors in RCC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / blood supply
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Endothelial Growth Factors / biosynthesis*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Kidney Neoplasms / blood supply
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Lymphokines / biosynthesis*
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Microcirculation
  • Middle Aged
  • Neovascularization, Pathologic*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9