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04 August 2015 : Clinical Research  

High VEGF-D and Low MMP-2 Serum Levels Predict Nodal-Positive Disease in Invasive Bladder Cancer

Tobias BenoitABCDEF, Etienne X. KellerB, Pirmin WolfsgruberB, Thomas HermannsCDE, Michele GünthartB, Irina BanzolaE, Tullio SulserE, Maurizio ProvenzanoCDE, Cédric PoyetCDEFG

DOI: 10.12659/MSM.894383

Med Sci Monit 2015; 21:2266-2274


BACKGROUND: To investigate stromal variables including angiogenesis, lymphangiogenesis, and matrix metalloproteinase (MMP) in the serum of patients with urothelial carcinoma of the bladder (UCB) and to evaluate their association with histopathological characteristics and clinical outcome.

MATERIAL AND METHODS: Protein levels of vascular endothelial growth factors-A, -C, -D (VEGF-A/-C/-D), their receptors- VEGF-R2 and -R3 (VEGF-R2/-R3), and matrix metalloproteinases 2, -3, and -7 (MMP-2, MMP-3, MMP-7) were quantified in the blood serum samples of 71 patients with UCB before radical cystectomy (RC). Samples of patients with non-invasive UCB or no history of UCB were investigated as controls (n=20). Protein levels in the serum were measured using a flow cytometric cytokine assay.

RESULTS: A positive association for VEGF-D (p<0.001) and an inverse association for MMP-2 (p=0.017) were observed in patients with positive lymph node (LN) status at the time of RC. VEGF-A (p<0.001), VEGF-C (p<0.001), MMP-2 (p<0.001), and MMP-7 (p=0.005) serum levels were different in serum of patients with invasive UCB compared with non-invasive UCB or healthy individuals. None of the serum markers were associated with disease progression.

CONCLUSIONS: High VEGF-D and low MMP-2 serum levels predict LN metastasis in patients with UCB at the time of RC. VEGF-A, VEGF-C, MMP-2, and MMP-7 serum levels varied significantly between invasive and non-invasive disease as well as in comparison with healthy individuals. Clinical implementation of these marker serum measurements may be valuable to select high-risk patients with more invasive or nodal-positive disease.

Keywords: Biomarkers, Tumor - blood, Aged, 80 and over, Case-Control Studies, Matrix Metalloproteinase 2 - blood, Predictive Value of Tests, Urinary Bladder Neoplasms - secondary, Vascular Endothelial Growth Factor D - blood

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750