OBJECTIVE To describe the
lymphatic vessel density and to determine the functional and
prognostic significance of
tumoral lymphatic vessels in upper tract urothelial
carcinoma (UTUC). PATIENTS AND METHODS The study included 65 patients who had a radical nephroureterectomy (RNU) for UTUC between 1997 and 2004. All
pathological slides were re-evaluated by one reference
pathologist and clinical data were reviewed.
Lymphatic endothelial cells (LECs) were stained immunohistochemically using D2-40. The
lymphatic vessel density (LVD) was described in representative intratumoral (ITLVD), peritumoral (PTLVD) and non-tumoral (NTLVD) areas.
Random samples were
selected for double-immunostaining with D2-40 and CD-34 (to distinguish
blood and
lymphatic vessels) and the proliferation marker Ki-67 to detect
lymphangiogenesis. The primary outcome measures were disease-specific survival (DSS) and disease recurrence (urothelial and/or distant). RESULTS The
median (
interquartile range) PTLVD was 4.0 (3.0-6.3), and significantly higher than that for ITLVD, of 0.3 (0-1.7) (P < 0.001), and NTLVD, of 3 (2.0-3.7) (P < 0.001). Both a higher ITLVD and PTLVD, the presence of lymphovascular invasion (LVI) (each P < 0.001) and a high
tumour grade (P = 0.004) were associated with reduced DSS on
univariate analysis. A higher PTLVD (P = 0.028) and the presence of LVI (P = 0.020) independently predicted reduced DSS on
multivariate analysis. IT and PT
lymphatic vessels showed proliferating LECs in all analysed samples. CONCLUSION
Lymphangiogenesis is present in UTUC, as shown by a significantly increased PTLVD and proliferating LECs. Our findings suggest functional relevance of PT
lymphatic vessels during
lymphatic tumour spread. PTLVD is a potential novel
prognostic factor for DSS in UTUC, and further
prospective studies will be needed to determine the effect of its routine evaluation on clinical outcomes of this malignancy.
