Evaluation of peri-operative peripheral and renal venous levels of pro- and anti-angiogenic factors and their relevance in patients with renal cell carcinoma.
OBJECTIVE
To evaluate peri-operative peripheral and renal venous plasma levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor type BB (PDGF-BB), transforming growth factor (TGF)-beta1, endostatin, and thrombospondin-1 (TSP-1) in relation to pathological variables and prognosis, as pro- and anti-angiogenic factors are important for tumour growth and treatment of patients with renal cell carcinoma (RCC).


METHODS
The study included 74 consecutive patients with sporadic RCC who had tumour nephrectomy. Peripheral venous blood was drawn 1 day before, immediately and 1, 3 and 5 days after surgery. Renal venous blood was collected in a subgroup of 33 patients during surgery. The variables were analysed using quantitative enzyme-linked immunoassay kits, and associated with pathological variables and disease-specific survival.


RESULTS
Soon after surgery, peripheral venous VEGF, PDGF-BB and TGF-beta1 levels were decreased, whereas endostatin levels were significantly increased. Renal venous VEGF, PDGF-BB and TGF-beta1 levels were higher than in the general venous blood pool. Renal venous VEGF levels were correlated with tumour diameter and associated with grade and vascular invasion. After a mean follow-up of 30 months, higher peripheral preoperative, early peripheral postoperative and renal venous VEGF levels were associated with a poorer prognosis. However, in a multivariate analysis only Tumour-Node-Metastasis stage and Eastern Cooperative Oncology Group performance status were independent prognosticators of disease-specific survival.


CONCLUSIONS
Circulating pro- and anti-angiogenic factors change early after nephrectomy. VEGF, PDGF-BB and TGF-beta1 are higher in the renal vein than in the general venous blood pool. Higher renal venous and peripheral levels of VEGF might be associated with a poorer prognosis.
Klatte
Tobias
T
Department of Urology, Otto-von-Guericke-Universität, Magdeburg, Germany. tklatte@mednet.ucla.edu
Böhm
Malte
M
Nelius
Thomas
T
Filleur
Stephanie
S
Reiher
Frank
F
Allhoff
Ernst Peter
EP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077214:Becaplermin; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000601:surgery; D043169:Endostatins; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000379:methods; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D020574:Proto-Oncogene Proteins c-sis; D019700:Thrombospondin 1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D043169:Endostatins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin