A comparison of plasma versus histologic indices of angiogenic markers in breast cancer.
BACKGROUND
Over-expression of angiogenic growth factors and their receptors, and high levels of these molecules in the blood, are a common feature of cancer although the relationships between cell expression and plasma levels are unknown. We hypothesized a significant correlation between the expression and cellular distribution of vascular endothelial growth factor (VEGF), its receptor Flt-1, and the angiopoietin receptor Tie-2 with levels of these molecules in the plasma.


METHODS
The tissue expression of VEGF, Flt-1, and Tie-2 were investigated by immunohistochemistry, and plasma levels assessed by enzyme-linked immunosorbent assay in 36 patients with breast cancer and 15 with benign breast disease.


RESULTS
Despite expected significant differences in plasma levels of the molecules (P<0.03 to <0.001), no significant differences were found in Tie-2, VEGF, and Flt-1 tissue expression between breast cancer and benign disease controls. No significant correlations were observed between plasma levels of their tissue expression.


CONCLUSIONS
Tissue expression of Tie-2, VEGF, and Flt-1 may not be an overly sensitive tool for assessing abnormalities of coagulation, platelet activation, and angiogenesis in human cancer. Plasma markers may not be representative of tumor activity, and may not come wholly from tumor cells. Instead these markers may be indicative of endothelial dysfunction in cancer patients.
Caine
Graham J
GJ
Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
Lip
Gregory
G
Zanetto
Ulyses
U
Maheshwari
Mahwandra
M
Stonelake
Paul S
PS
Blann
Andrew D
AD
D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000473:pathology; D042787:Receptor, TIE-2 / Q000032:analysis / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000097:blood*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1