Lymphatic vessel density as a predictor of lymph node metastasis and its relationship with prognosis in urothelial carcinoma of the bladder

Level of Evidence 4 What's known on the subject? and What does the study add? VEGF-C has been found up-regulated in some kind of tumour tissues. In this study, we found that the expression of VEGF-C was also increased in bladder cancer. The increase of VEGF-C may have an influence on lymphatic node metastasis of bladder cancer. OBJECTIVE center dot To determine the correlation of lymphatic vessel density (LVD) with lymph node metastasis (LNM), investigate the impact of vascular endothelial growth factor (VEGF)-C mRNA expression on LVD, and evaluate the impact of LVD on prognosis of bladder urothelial carcinoma (BUC). PATIENTS AND METHODS center dot In 56 samples of BUC, the lymphatic vessels were immunostained with polyclonal antibodies against VEGF receptor 3 (VEGFR-3). LVD was evaluated in both intratumoural and peritumoural tissues. center dot The expression level of VEGF-C mRNA was assessed by reverse transcriptase-polymerase chain reaction. center dot The correlation of LVD with VEGF-C mRNA and other clinicopathological parameters was also investigated. RESULTS center dot VEGFR-3 was expressed in lymphatic vessel endothelial cytoplasm. As the expression level of VEGF-C became higher, the intratumoural and peritumoural LVD increased significantly (P < 0.05). center dot At the same time, increased intratumoural and peritumoural LVD also presented in patients with lymphatic vessel invasion and LNM of BUC (P < 0.05). center dot In addition, increased peritumoural LVD and LNM predicted a poor recurrence-free survival (P < 0.05). CONCLUSIONS center dot It is suggested that in BUC, VEGF-C expression may contribute to lymphangiogenesis. center dot Patients with high peritumoural LVD and LNM tend to have a poor prognosis. center dot Inhibition of the blocking VEGF-C/VEGFR-3 pathway may attenuate lymphangiogenesis and represent a new target for investigational treatment of urothelial carcinoma of the bladder.