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

Abstract

Objective: • 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: • 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. • The expression level of VEGF-C mRNA was assessed by reverse transcriptase-polymerase chain reaction. • The correlation of LVD with VEGF-C mRNA and other clinicopathological parameters was also investigated.

Results: • 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). • At the same time, increased intratumoural and peritumoural LVD also presented in patients with lymphatic vessel invasion and LNM of BUC (P < 0.05). • In addition, increased peritumoural LVD and LNM predicted a poor recurrence-free survival (P < 0.05).

Conclusions: • It is suggested that in BUC, VEGF-C expression may contribute to lymphangiogenesis. • Patients with high peritumoural LVD and LNM tend to have a poor prognosis. • 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.