title: The role of lymph vessel density and lymphangiogenesis in metastatic tumor spread of nonseminomatous testicular germ cell tumors.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: julia.heinzelbecker@umm.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Heinzelbecker
authors.affiliation: Department of Urology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gropp
authors.affiliation: Institute of Medical Statistics and Biometry, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.affiliation: Institute of Pathology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Huettl
authors.affiliation: Institute of Pathology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stroebel
authors.affiliation: Department of Urology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haecker
authors.affiliation: Department of Urology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.affiliation: Department of Urology, University Medical Centre Göttingen, Georg-August University, Göttingen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Trojan
mesh_terms: D000328:Adult; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008297:Male; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D013736:Testicular Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; C119248:LYVE1 protein, human; D033921:Vesicular Transport Proteins
keywords: Lymph vessel density (LVD); Lymphangiogenesis; Lymphovascular invasion; Metastases; NSGCT; Testicular cancer