Factors influencing tissue concentration of vascular endothelial growth factor in colorectal carcinoma.
OBJECTIVE
Vascular endothelial growth factor (VEGF) promotes proliferation of various tumor cells by stimulating angiogenesis. Experimentally, hypoxia and energy depletion are known to induce angiogenesis by increasing VEGF expression. We investigated whether factors reflecting the general condition of the patients influence the tissue concentration of VEGF in colorectal carcinoma.


METHODS
Tissue concentrations of VEGF in 81 colorectal carcinomas, 81 normal mucosas, and 30 colonic adenomas were determined. The expressions of VEGF and its receptor in cancer tissue were evaluated immunohistochemically. For the assessment of the general preoperative condition of the patients, the nutritional status was evaluated and arterial blood gas was analyzed.


RESULTS
The mean concentration of VEGF in the cancer tissue was significantly higher than that in the normal colonic mucosa and colonic adenoma. Tumor size, histological grade, serum cholinesterase, and arterial level of PO2 were the independent factors that influenced the tissue concentration of VEGF in colorectal cancer. Immunohistochemically, the VEGF-positive cancer tended to have an increased expression of VEGF receptor, kinase insert domain-containing receptor (KDR). In patients with positive KDR in the tumor, the arterial levels of PO2 and O2 saturation were significantly lower than those in patients without its expression.


CONCLUSIONS
Tissue content of VEGF or expression of KDR in colorectal carcinoma may be associated with disease status, including nutritional status, systemic oxygenation, and tumor progression. The systemic-local regulating mechanism of VEGF or KDR may play an important role in the constant growth of tumor cells, especially in wasted colorectal cancer patients.
Ono
T
T
Department of Surgery II, Mie University Medical School, Tsu, Japan.
Miki
C
C
D000230:Adenocarcinoma / Q000473:pathology*; D000236:Adenoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000502:physiology; D015179:Colorectal Neoplasms / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor