Lymphangiogenesis occurs in upper tract urothelial carcinoma and correlates with lymphatic tumour dissemination and poor prognosis

BJU International - Tập 103 Số 8 - Trang 1040-1046 - 2009
Christian Bolenz1, Mario I. Fernández2, Lutz Trojan1, Katja Hoffmann1, Edwin Herrmann3, Annette Steidler1, Christel Weiß1, Philipp Ströbel4, P. Alken1, Maurice Stephan Michel1
1Departments of Urology, Medical Statistics and
2Clinica Alemana, Santiago, Chile
3University of Münster, Münster, Germany, and
4Pathology, Mannheim Medical Center, University of Heidelberg, Mannheim,

Tóm tắt

OBJECTIVETo 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 METHODSThe 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).RESULTSThe 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.CONCLUSIONLymphangiogenesis 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.

Từ khóa


Tài liệu tham khảo

10.1200/JCO.2005.05.516

10.1016/j.juro.2006.08.004

10.1002/cncr.22970

10.1038/nature04480

10.1158/0008-5472.CAN-04-2475

10.1016/S0022-5347(06)00520-9

10.1097/01.ju.0000181801.22474.8b

10.1016/j.it.2004.05.003

10.1200/JCO.2004.00.3467

10.1158/1078-0432.CCR-05-1284

Herrmann E, 2007, VEGF‐C, VEGF‐D and Flt‐4 in transitional bladder cancer: relationships to clinicopathological parameters and long‐term survival, Anticancer Res, 27, 3127

10.1038/nrm2183

10.1016/j.eururo.2007.08.030

10.1016/S0002-9440(10)62311-5

10.1007/s00292-004-0693-6

10.1016/S0002-9440(10)64328-3

10.1002/path.1776

10.1158/1078-0432.CCR-05-1077

10.1002/pros.20288

10.1007/s00428-006-0166-9

UICC., 2002, TNM Classification of Malignant Tumours

10.1097/00000478-199812000-00001

10.1097/01.ju.0000128860.00639.9c

10.1016/j.eururo.2004.04.011

10.1158/1078-0432.CCR-05-1142

10.1111/j.1749-6632.2002.tb04873.x

10.1126/science.1071420

10.1002/path.1343

10.1097/01.pas.0000174269.99459.9d

10.1038/sj.bjc.6603445

Thông tin
Thông tin xuất bản

BJU International

Tập 103 Số 8

1040-1046

Thông tin tác giả