title: Microvascular invasion of testicular nonseminomatous germ cell tumors: implications of separate evaluation of lymphatic and blood vessels.
abstract: OBJECTIVE
  We separately evaluated the lymphatic and blood vascular systems to assess the diagnostic accuracy of microvascular invasion and identify predictive markers for occult metastasis of testicular nonseminomatous germ cell tumors.
  
  
  METHODS
  Tissue samples of 86 patients treated for testicular nonseminomatous germ cell tumors (stage 1 in 48 and stage greater than 1 in 38) were stained using the lymphatic endothelial cell specific marker LYVE-1 and the blood vessel endothelial cell marker von Willebrand factor. We assessed lymph vessel density in LYVE-1 stained sections and blood vessel density in von Willebrand factor stained sections. Lymphovascular invasion in LYVE-1 stained sections and blood vascular invasion in von Willebrand factor stained sections were documented. Parameters were correlated with standard clinicopathological data.
  
  
  RESULTS
  Blood vessel density in von Willebrand factor sections was significantly greater than lymphatic vessel density in LYVE-1 sections (p<0.001). Peritumor and nontumor lymphatic vessel density in LYVE-1 sections was associated with metastasis at diagnosis (OR 1.277/U, p=0.020 and OR 1.113/U, p=0.095). Lymphovascular invasion in LYVE-1 sections was significantly associated with metastasis (OR=4.517, p=0.002) but blood vascular invasion in von Willebrand factor sections was only slightly significant (OR 2.261, p=0.071). Only lymphovascular invasion in LYVE-1 stained sections was significantly associated with metastasis in a multiple logistic regression model. Microvascular invasion in hematoxylin and eosin stained sections was not associated with metastasis but microvascular invasion evaluated in LYVE-1 and von Willebrand factor stained sections was associated with metastasis (OR 3.506, p=0.016).
  
  
  CONCLUSIONS
  Lymphovascular invasion in LYVE-1 stained sections was the most important predictive parameter for metastasis at diagnosis, suggesting greater relevance of the lymphatic system in metastatic dissemination of testicular nonseminomatous germ cell tumors. Vascular endothelial cell specific markers provide higher diagnostic accuracy for microvascular invasion. Our results may impact the current concept of microvascular invasion used for risk stratification of clinical stage 1 testicular nonseminomatous germ cell tumors.
authors.affiliation: Department of Urology, University Medical Centre 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 Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gross-Weege
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: Christian
authors.initials: C
authors.lastname: Hörner
authors.affiliation: Institute of Pathology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Trunk
authors.affiliation: Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Erben
authors.affiliation: Department of Urology, University Medical Centre 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 Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
mesh_terms: D006801:Humans; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels; D008297:Male; D055806:Microvessels; D009361:Neoplasm Invasiveness; D009373:Neoplasms, Germ Cell and Embryonal / Q000473:pathology*; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000473:pathology*; D019043:Vascular Neoplasms / Q000473:pathology*
keywords: blood vessels; lymphatic system; neoplasm metastasis; nonseminomatous germ cell tumor; testis