Histologic features of venous invasion, expression of vascular endothelial growth factor and matrix metalloproteinase-2 and matrix metalloproteinase-9, and the relation with liver metastasis in pancreatic cancer

Pancreas. 2002 Mar;24(2):169-78. doi: 10.1097/00006676-200203000-00008.


Introduction: Pancreatic cancer frequently is associated with venous invasion and hematogenous metastasis.

Aims: To determine morphologic features of invaded veins, intratumoral vascular composition, the correlation with liver metastasis, and expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and MMP-9, and the mechanism of development of hematogenous metastasis.

Methodology: We examined 32 patients with resected pancreatic cancer: 18 had postoperative liver metastasis, and 14 had no liver metastasis. Specimens were examined to determine the composition of veins and microvessels by staining of victoria-blue and CD34. We also investigated expression of VEGF, MMP-2, and MMP-9 by immunohistochemical staining.

Results: Venous invasion was detected in 31 of 32 patients. Invaded venous densities of middle- and large-sized veins were significantly higher in patients with liver metastasis than in those with nonliver metastasis, and they were related to MMP-2 and MMP-9 overexpression. Invaded veins with fragmentation of the lumen through cancer cells were considered to be an intravasation of cancer (destroyed type vein), and their numbers were significantly related to liver metastasis, and MMP-2 and MMP-9 overexpression.

Conclusion: In conclusion, almost all the patients with pancreatic cancer showed venous invasion, indicating that invasion into large veins and destroyed type veins could be a risk factor for liver metastasis and that increased expression MMP-2 and MMP-9 were related to such invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / biosynthesis*
  • Female
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Lymphokines / analysis
  • Lymphokines / biosynthesis*
  • Male
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Microcirculation / pathology
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Veins / pathology


  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9