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

• Published in: Urologic oncology 2014-02, Vol.32 (2), p.178-185
• Main Authors: Heinzelbecker, Julia, M.D, Gropp, Tobias, Weiss, Christel, Ph.D, Huettl, Katrin, M.D, Stroebel, Philipp, M.D, Haecker, Axel, M.D, Bolenz, Christian, M.D, Trojan, Lutz, M.D
• Format: Article
• Language: English
• Subjects: Adult; Endothelial Cells - metabolism; Humans; Immunohistochemistry; Ki-67 Antigen - metabolism; Lymph vessel density (LVD); Lymphangiogenesis; Lymphatic Vessels - metabolism; Lymphatic Vessels - pathology; Lymphovascular invasion; Male; Metastases; Multivariate Analysis; Neoplasm Metastasis; Neoplasms, Germ Cell and Embryonal - diagnosis; Neoplasms, Germ Cell and Embryonal - metabolism; Neoplasms, Germ Cell and Embryonal - pathology; NSGCT; Prognosis; Testicular cancer; Testicular Neoplasms - diagnosis; Testicular Neoplasms - metabolism; Testicular Neoplasms - pathology; Urology; Vesicular Transport Proteins - metabolism; Young Adult
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2012.08.004

Abstract 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 stainings 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.