The role of lymph vessel density and lymphangiogenesis in metastatic tumor spread of nonseminomatous testicular germ cell tumors.

Objectives: To evaluate the role of lymph vessel density (LVD) and lymphangiogenesis in nonseminomatous testicular germ cell tumors (NSGCT) using the specific lymphatic endothelial cell (LEC) marker LYVE-1. Materials and methods: NSGCT specimens of 77 patients (32 with and 45 without metastases) were stained immunohistochemically using a:LYVE-1 antibody. LVD was measured in different representative areas by the standardized "hot spot" method. Fluorescence double staining for LYVE-1 and Ki-67 were performed. The median follow-up period was 46 (range 3-170) months. Results: The mean peritumoral (2.16 +/- 2.17) and nontumoral LVD (3.17 +/- 3.24) were significantly higher than intratumoral LVD (0.16 +/- 0.73) (both: P = < 0.001). In 5 patients proliferating LECs were observed. The peritumoral LVD was 2.66 (+/- 2.31) and 1.80 (+/- 2.02) in metastatic and nonmetastatic NSGCT, respectively. A higher peritumoral LVD was associated with the presence of metastases at the time of diagnosis (P = 0.087). The mean peritumoral LVD in tumors with and without lymphovascular invasion (LVI) was 3.33 (+/- 2.20) and 1.62 (+/- 1.95), respectively (P < 0.001). The presence of LVI detected by LYVE-1 (LVI-LYVE-1) was independently associated with metastatic disease (logistic regression; P = 0.045). Conclusions: The presence of a high peritumoral LVD and LVI-LYVE-1 are both associated with metastatic disease in NSGCT. LVI-LYVE-1 was independently associated with the presence of metastases at the time of diagnosis. Proliferating LECs are present, suggesting that lymphangiogenesis may promote metastatic dissemination of tumor cells in NSGCT. (C) 2014 Elsevier Inc. All rights reserved.