VEGF-C, VEGF-D and Flt-4 in transitional bladder cancer: relationships to clinicopathological parameters and long-term survival.
BACKGROUND
Our aim was to determine the role of the lymphangiogenic markers VEGF-C, VEGF-D and Flt-4 in transitional bladder cancer.


METHODS
Archival cystectomy tumor blocks of 286 patients were selected for construction of a tissue microarray (TMA). Paraffin sections were assessed immunohistochemically using polyclonal antibodies against VEGF-C, VEGF-D and Flt-4. Staining results were evaluated semiquantitatively and analyzed for their association with various clinicopathological factors.


RESULTS
There was no association of VEGF-C with histopathological parameters or clinical outcome. Patients with VEGF-D overexpression had higher pathological tumor stages (p =0.021) and regional lymph node metastasis (p=0.008). Furthermore, they had a significantly reduced disease-free survival (p=0.042). Overexpression of Flt-4 was particularly present in the subgroup of G3 and G4 tumors (p=0.001) and was associated with a shorter disease-free survival (p=0.041). In multivariate analysis, only tumor stage and lymph node metastasis were independent prognostic parameters.


CONCLUSIONS
Targeting VEGF-D and Flt-4 could be a useful tool to predict and control progression of bladder cancer.
Herrmann
Edwin
E
Department of Urology, University of Münster, Münster, Germany. herrmae@ukmuenster.de
Eltze
Elke
E
Bierer
Stefan
S
Köpke
Thomas
T
Görge
Tobias
T
Neumann
Jorg
J
Hertle
Lothar
L
Wülfing
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D015653:Cystectomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis*
D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3