Prognostic implications of lymphangiogenesis in muscle-invasive transitional cell carcinoma of the bladder.
OBJECTIVE
Aim of the study was to describe and evaluate the association of lymph vessel density with clinicopathological parameters and survival in patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder.


METHODS
The data on 108 patients with muscle-invasive bladder TCC, who underwent radical cystectomy, were reviewed retrospectively. Sections were analysed immunohistochemically for D2-40, a specific lymphatic endothelial cell (LEC) marker. Counts of lymph vessels were taken in intratumoural and peritumoural areas as well as in normal tissue. To detect proliferating LECs, we performed a double immunostaining for D2-40 and the proliferation marker Ki-67.


RESULTS
Peritumoural vessels were observed in 105 (97.2%) sections and intratumoural vessels in 65 (60.2%). Higher intratumoural lymph vesseI density (LVD) correlated significantly with poor histological differentiation (p=0.01). Higher peritumoural LVD showed a significant association with the presence of lymph node metastasis (p=0.0004). However, LVDs had no statistically significant influence on survival. Intratumoural and peritumoural lymph vessels showed proliferating LECs in varying proportions in all examined samples.


CONCLUSIONS
The present study is the first to suggest the existence of proliferating lymph vessels, and, therefore, of lymphangiogenesis in bladder TCC. To our knowledge, it is also the first to confirm a strong correlation of higher peritumoural LVD with the presence of lymph nodes in clinically localized invasive bladder TCC. These findings indicate that lymphangiogenesis may contribute to tumour dissemination and thus provide a potential target for bladder cancer therapy.
Fernández
Mario I
MI
Department of Urology, University Hospital Mannheim, Germany.
Bolenz
Christian
C
Trojan
Lutz
L
Steidler
Annette
A
Weiss
Christel
C
Alken
Peter
P
Grobholz
Rainer
R
Michel
Maurice Stephan
MS
D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002452:Cell Count; D015653:Cystectomy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery