[New markers for pharmacological targeting in bladder cancer with lymph node metastasis].
OBJECTIVE
VECF-C, -D and their receptor Flt-4 are associated with lymph node metastasis and a poor prognosis in many tumour entities. We have analysed the expression of these factors in transitional cell carcinoma of the bladder with positive lymph nodes.


METHODS
We constructed "tissue microarrays" (TMAs) from bladder cancer specimens (BC-array) and corresponding lymph node metastases (LN-array) of 73 patients, who all underwent radical cystectomy and bilateral lymphadenectomy. After immunohistochemical staining, semiquantitative analysis was performed using polyclonal antibodies for VEGF-C, -D and Flt-4. The results were correlated with various histopathological and clinical variables.


RESULTS
VEGF-C (p = 0.007) and Flt-4 (p = 0.019) were significantly higher expressed in the LN-array compared to the BC-array. In the LN-array VEGF-D correlated with T-(p = 0.013) and N-stage (p = 0.030) Flt-4 correlated with N-stage (p = 0.011) and distant metastasis (p = 0.011) in the BC-array, as well as with T-(p = 0.004) and N-stage (p = 0.014) in the LN-array. Accordingly, in the LN-array VEGF-D positive patients showed both a shorter disease-free survival (p = 0.028) and a poorer overall survival (p = 0.014). Similarly, Flt-4 positive patients had a shorter overall survival (p = 0.033).


CONCLUSIONS
Patients with transitional bladder cancer and lymph node metastasis have a poorer prognosis when they overexpress VEGF-D and Flt-4 in their lymph nodes. Pharmacological targeting of these factors could improve their overall survival.
Herrmann
E
E
Klinik und Poliklinik für Urologie, Universitätsklinikum Münster, Germany. herrmae@ukmuenster.de
Eltze
E
E
Köpke
T
T
Bolenz
C
C
Bierer
S
S
Neumann
J
J
Hertle
L
L
Wülfing
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015653:Cystectomy; D003627:Data Interpretation, Statistical; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013997:Time Factors; D046888:Tissue Array Analysis; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3