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


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Nagakawa
Yuichi
Y
Department of Surgery, Tokyo Medical University, 6-7-012 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. naga@tokyo-med.ac.jp
Aoki
Tatsuya
T
Kasuya
Kazuhiko
K
Tsuchida
Akihiko
A
Koyanagi
Yasuhisa
Y
D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis*; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014680:Veins / Q000473:pathology
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9