Bolenz Christian, Fernández Mario I, Trojan Lutz, Hoffmann Katja, Herrmann Edwin, Steidler Annette, Weiss Christel, Ströbel Philipp, Alken Peter, Michel Maurice Stephan
Department of Urology, Mannheim Medical Center, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
BJU Int. 2009 Apr;103(8):1040-6. doi: 10.1111/j.1464-410X.2008.08135.x. Epub 2008 Oct 17.
To describe the lymphatic vessel density and to determine the functional and prognostic significance of tumoral lymphatic vessels in upper tract urothelial carcinoma (UTUC).
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).
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.
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.
描述淋巴管密度，并确定上尿路尿路上皮癌（UTUC）中肿瘤淋巴管的功能及预后意义。
本研究纳入了1997年至2004年间因UTUC接受根治性肾输尿管切除术（RNU）的65例患者。所有病理切片由一名参考病理学家重新评估，并回顾临床资料。使用D2-40对淋巴管内皮细胞（LEC）进行免疫组织化学染色。在具有代表性的肿瘤内（ITLVD）、肿瘤周围（PTLVD）和非肿瘤（NTLVD）区域描述淋巴管密度。随机选取样本进行D2-40和CD-34双重免疫染色（以区分血管和淋巴管）以及增殖标志物Ki-67染色，以检测淋巴管生成。主要观察指标为疾病特异性生存（DSS）和疾病复发（尿路上皮和/或远处复发）。
PTLVD的中位数（四分位间距）为4.0（3.0 - 6.3），显著高于ITLVD的0.3（0 - 1.7）（P < 0.001）和NTLVD的3（2.0 - 3.7）（P < 0.001）。单因素分析显示，较高的ITLVD和PTLVD、存在淋巴管侵犯（LVI）（各P < 0.001）以及高肿瘤分级（P = 0.004）均与DSS降低相关。多因素分析显示，较高的PTLVD（P = 0.028）和存在LVI（P = 0.020）独立预测DSS降低。在所有分析样本中，肿瘤内和肿瘤周围淋巴管均显示LEC增殖。
UTUC中存在淋巴管生成，表现为PTLVD显著增加和LEC增殖。我们的研究结果表明肿瘤周围淋巴管在肿瘤淋巴转移过程中具有功能相关性。PTLVD是UTUC中DSS的一个潜在新预后因素，需要进一步的前瞻性研究来确定其常规评估对这种恶性肿瘤临床结局的影响。
